Plasma fatty acid changes following consumption of dietary oils containing n3, n6, and n9 fatty acids at different proportions: preliminary findings of the Canola Oil Multicenter Intervention Trial (COMIT)

The Canola Oil Multicenter Intervention Trial (COMIT) was a randomized controlled crossover study designed to evaluate the effects of five diets that provided different oils and/or oil blends on cardiovascular disease (CVD) risk factors in individuals with abdominal obesity. The present objective is to report preliminary findings on plasma fatty acid profiles in volunteers with abdominal obesity, following the consumption of diets enriched with n3, n6 and n9 fatty acids. COMIT was conducted at three clinical sites, Winnipeg, Manitoba, Canada, Québec City, Québec, Canada and University Park, Pennsylvania, United States. Inclusion criteria were at least one of the following: waist circumference (greater equal to 90 cm for males and greater equal to 84 cm for females), and at least one other criterion: triglycerides greater equal to 1.7 mmol/L, high density lipoprotein cholesterol less 1 mmol/L (males) or less 1.3 mmol/L (females), blood pressure greater equal to 130 mmHg (systolic) and or greater equal to 85 mmHg (diastolic), and glucose greater equal to 5.5 mmol/L. Weight maintaining diets that included shakes with one of the dietary oil blends were provided during each of the five 30 day dietary phases. Dietary phases were separated by four week washout periods. Treatment oils were canola oil, high oleic canola oil, high oleic canola oil enriched with docosahexaenoic acid (DHA), flax oil and safflower oil blend, and corn oil and safflower oil blend. A per protocol approach with a mixed model analysis was decided to be appropriate for data analysis. One hundred and seventy volunteers were randomized and 130 completed the study with a dropout rate of 23.5 percent. The mean plasma total DHA concentrations, which were analyzed among all participants as a measure of adherence, increased by more than 100percent in the DHA enriched phase, compared to other phases, demonstrating excellent dietary adherence.
Recruitment and retention strategies were effective in achieving a sufficient number of participants who completed the study protocol to enable sufficient statistical power to resolve small differences in outcome measures. It is expected that the study will generate important data thereby enhancing our understanding of the effects of n3, n6, and n9 fatty acid containing oils on CVD risks. (Authors abstract)

Background

It is well established that decreasing dietary saturated fatty acids (SFA) reduces the risk of cardiovascular disease (CVD). A controversy is the debate surrounding alpha linolenic acid (ALA). Whether its effects are dependent on its conversion to longer chain n3 fatty acids needs to be better substantiated. The relative efficacy of different classes of PUFA, specifically linoleic acid (LA), ALA and docosahexaenoic acid (DHA), in modulating inflammatory processes and endothelial function also remains to be elucidated. A direct comparison of dietary n6 with n3 fatty acids on inflammatory biomarkers and endothelial function would also be helpful in clarifying these issues.

Different classes of fatty acids appear to have different effects on body fat accretion. A need also exists to evaluate the effects of various fatty acid classes on body composition and body fat distribution.  A multicenter randomized clinical trial was designed to evaluate the biological effects of conventional canola oil, high oleic canola oil, DHA enriched high oleic canola oil, a blend of flax oil with safflower oil, and a blend of corn oil and safflower oil.  The contrast selected allowed for comparisons of the effects of oils rich in n9 versus n3 and n6 oil blends.
Circulating lipids and/or lipoproteins, inflammatory biomarkers, endothelial function and body composition were evaluated after each dietary treatment period. Additionally, mechanistic assessments including reverse cholesterol transport, stable isotope fatty acid conversion, and fatty acid desaturase genetic variation analysis were also carried out. Consequently, the purpose of this study was to comprehensively investigate the effects of major fatty acid classes on biomarkers of chronic disease at a mechanistic level. This paper describes the protocol and
subject recruitment experience for the COMIT study and presents plasma fatty acid data.

The recruitment and retention strategies employed resulted in the successful completion of the required number of participants. Predictable elevations of specific plasma fatty acids representing the major dietary fatty acids in the intervention oils were observed as expected. For example, the three-fold elevation of plasma ALA following the FlaxSaff dietary phase compared to the CornSaff dietary phase demonstrated the ability of flax oil enriched shakes to raise serum ALA levels. Similarly, the 1.3 fold elevation of oleic acid after the Canola Oleic treatment compared to CornSaff treatment is consistent with its high oleic acid content. Significantly higher eicosapentaenoic acid (EPA) levels in Canola and FlaxSaff compared to other treatments are evidence for the metabolic conversion of ALA to EPA. The significant elevation of EPA in CanolaDHA compared to other treatments (except FlaxSaff) could probably be due to the higher EPA content in the algal sourced DHA that was used in this study. However DHA might convert back to EPA in CanolaDHA, which can be further confirmed by the stable isotope trafficking assays in this study. Lack of a DHA raising effect of FlaxSaff treatment agrees with prior work demonstrating low efficiency of conversion of ALA to DHA.

The final sample size of 130 allowed detection of a difference of 9.4 percent or greater in the RHI, which is a measure of the endothelial function, and a 10 percent difference of LDL-C with a power of 0.8 at a significance of 0.05.  Standardized protocols and efforts to minimize variation are expected to lead to findings that will help to fill the gaps in knowledge of the metabolism, lipid trafficking, and clinical efficacy of the major classes of dietary fatty acids. (Editors comments)