The present study suggests that a relatively short dietary intervention with refined olive oil can have a significant effect on plasma IL-6. In contrast, canola oil may impact plasma Lp-PLA2 mass without changing lipoproteins and other inflammatory biomarkers in patients referred to coronary angiography.
In the present study, the consumption of olive oil had a more lowering effect on plasma IL-6 concentration. The difference in plasma IL-6 levels between the two groups can be related to the difference in fatty acid composition of canola and olive oils. In particular, olive oil consists of 14.5% SFA, 70% oleic acid, 11% linoleic acid, and 1.5% palmitoleic acid, whereas canola oil is characterized by a low level of SFAs (7%); 61% oleic acid, 19% linoleic acid, and 9% alpha-linolenic acid (ALA) . Compared to canola oil, the amount of oleic and palmitoleic acid in olive oil is higher. In vitro studies have shown that the addition of oleic or palmitoleic acid to the cell culture medium is effective in reducing or preventing the increase of IL-6 levels [23-26]. Some human studies have shown evidence of an inverse association between oleic acid and IL-6 concentration .
A growing body of evidence indicates that Lp-PLA2 represents an independent risk factor for CVD. Lp-PLA2 belongs to the family of structurally diverse phospholipase A2 enzymes, also known as platelet-activating factor acetylhydrolase (PAF-AH) . Circulating Lp-PLA2 is primarily associated with LDL-C; the majority of it is bound to atherogenic small-dense LDL-C particles . In the present study, the consumption of CO reduced plasma Lp-PLA2 mass but not of its activity. Previous studies have shown a modest correlation between Lp-PLA2 mass and activity (30, 31). It has been suggested that Lp-PLA2 is associated with LDL-C in plasma, and this may results in the under-detection of the Lp-PLA2 mass by the ELISA method (32). However, since all study samples were measured in the same way in the current study, possible under-detection of the Lp-PLA2 mass was the same for the baseline and final samples. Despite this, both the Lp-PLA2 mass and activity are predictors of CVD events (33, 34). It has been shown that tocopherols could inhibit Lp-PLA2 activity . The amount of alpha-tocopherol in olive and canola oils is similar. However, canola oil is richer in gamma-tocopherol . The higher gamma-tocopherol content of canola oil may have an effect on the observed effect on Lp-PLA2. The observed decrease in the Lp-PLA2 level following CO consumption may also be related to its n-3 fatty acid content. Canola oil contains more PUFAs (both n-6 and n-3) and less MUFA than olive oil. In patients admitted to elective coronary angiography, the content of the long-chain n-3 PUFA eicosapentaenoic acid (EPA) in adipose tissue was inversely associated with plasma Lp-PLA2 mass . Similarly, in participants of the Multi-Ethnic Study of Atherosclerosis, plasma Lp-PLA2 mass and activity were significantly lower in those with the higher plasma EPA and Docosahexaenoic acid (DHA) . The evidence from intervention trials for the influence of n-3 PUFAs on Lp-PLA2 is equivocal. In healthy people, two studies have reported no effect of n-3 PUFA supplementation on Lp-PLA2 [34, 35]. Nelson et al. showed that supplementation with n-3 fatty acids capsules (fish oil or flaxseed oil) over 8 weeks had no significant effect on plasma Lp-PLA2 mass or activity when compared to control (olive oil capsule supplementation) . In contrast, Asztalos et al. showed that as compared to placebo (6 g/day olive oil) supplementation with the higher dose of EPA (1800 mg), but not DHA or lower dose of EPA (600 mg) over 6 weeks could reduce Lp-PLA2 mass in a healthy population . Apart from the effects in healthy subjects, an increase in n-3 intake has been shown to decrease Lp-PLA2 levels in patients with cardiovascular risk factors. In stable CAD patients undergoing percutaneous coronary intervention, administration of omega-3 PUFA (1 g/day) for 4 weeks decreased Lp-PLA2 mass and activity compared to control (soybean oil capsules) . Similar findings have been observed in patients with diabetes  and subjects who had residual hypertriglyceridemia after receiving statins [39, 40].
The pro-atherogenic role of Lp-PLA2 could be related to its ability to hydrolysis of oxidized phospholipids on the LDL-C surface, resulting in the generation of two proinflammatory and proapoptotic lipid mediators, lysophosphatidylcholine, and oxidized free fatty acids, which play an important role in the development of atherosclerotic necrotic cores by recruiting and activating macrophages or leukocytes . In the present study, although canola oil reduced the Lp-PLA2 level, it had no significant effect on inflammatory factors. Consistent with this contention, supplementation with n-3 fatty acids (EPA) has reduced plasma Lp-PLA2 without significant effects on plasma inflammatory biomarkers, including IL-6 .
Complement factors C3 and C4 have been associated with atherosclerosis and cardiovascular risk factors  and have shown substantial correlations with cardiovascular risk factors . Plasma C3 and C4 did not change in either group. In a previous study, an increase was observed in the C3 concentrations after the intake of high saturated fat, compared with high-monounsaturated fat .
In the current study, neither olive oil nor canola oil consumption had significantly impacted on plasma lipids and lipoproteins. Consistent with our findings, in previous studies, the intake of refined OO (60 g/day) has not had a significant effect on the plasma TG, LDL-C, or HDL-C levels in mildly hypercholesterolemic subjects who were not on lipid-lowering medications  or in stable coronary artery disease patients (50 mL/day) . However, some previous studies have reported the beneficial effects of CO on plasma lipids [45-48]. Yet, it should be noted that the study population in these studies were healthy people or those with cardiovascular risk factors, not on lipid-lowering agents. In contrast, most of the participants in the present study were under statin therapy and had an optimum level of plasma lipids. Therefore, the beneficial effects of canola oil on plasma lipid profiles appear to be evident in patients whose plasma lipids are high at baseline and are not on lipid-lowering medication. Intake of CO or OO in the context of a lipid-lowering diet for 3.5 weeks in hyperlipidemic subjects who were not on lipid-lowering agents had similar effects on serum lipoprotein concentration .
Study strengths and limitations
Comparison of two commonly consumed edible oils and detailed data collection were strengths of the current study. However, the present study has also some limitations. In the study, there was no run-in period. Since participants received dietary advice on a heart-healthy diet at baseline, effects due to the changes in dietary habits could not be excluded and part of the observed effects on investigated biomarkers may be related to dietary habits modification. However, participants of both groups received similar dietary advice and the potential effects were present in both groups. The duration of dietary intervention was relatively short. Furthermore, some participants were lost to follow-up and, or discontinued the intervention, which reduced the final sample size. In addition, we were unable to blind the participants because of the sensory and appearance characteristics of the two oils. Moreover, we could not conduct the study in a tightly regulated, controlled feeding design. However, the study oils were provided to individuals (more than each participant's need), and their consumption was monitored weekly. Besides, since most of the participants were male, the sample cannot be considered representative, and this may limit the findings to a specific sex. Furthermore, cross-over study design could have reduced confounding factors associated with the inherited characteristics of the participants. Nevertheless, cross-over studies require that study participants be followed for a more extended period and that their treatment plan should not change during this time. Moreover, given that most of the population spends most of their time in the postprandial state, measurements of postprandial lipids and inflammatory markers could have provided additional information on potential changes in cardiovascular risk.