Drs Puri and Richardson raise an interesting question regarding our choice of olive oil as a placebo. They correctly state that olive oil contains a relatively high concentration of oleic acid, an ω9 fatty acid. They also correctly point out that oleic acid can be converted in vivo to oleamide. Oleamide (cis-9,10-octadecenoamide) is a fatty-acid amide with measurable neurobiological effects in animals, including sedation and modulation of several serotonin receptor subtypes.1 The clinical significance, concentration, and control mechanisms for the biosynthesis of oleamide in humans remain unknown.2 However, since depot fat in the human body contains approximately 50% oleic acid,3 a typical 70-kg human with 22% body fat would have at least 7 kg of total oleic acid in various cellular and tissue compartments. This excess of precursor oleic acid suggests that the amount of oleic acid is likely not crucial to the rate of biosynthesis of olemide. A daily dose of 9.6 g of olive oil (supplying 5-7 g of oleic acid), such as we used in our study, would equal only about 0.1% of the total oleic acid stores in the body. Thus, it seems unlikely that the olive oil used in our study produced any appreciable change in olemide concentration. However, we do agree with Drs Puri and Richardson that the choice of placebo is an important and difficult decision in clinical studies of fatty acids, and that this issue requires more study.
Stoll AL, Marangell L, Severus WE. The Effects of Olive Oil on ω3 Fatty Acids and Mood Disorders. Arch Gen Psychiatry. 2000;57(7):715. doi: