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Effect of omega-3, omega-6 and omega-9 fatty acids on cardiovascular risk in adults: primary prevention clinical trial.

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Caroline Pappiani
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Saúde Pública (FSP/CIR)
Defense date:
Examining board members:
Nágila Raquel Teixeira Damasceno; Inar Alves de Castro; Maria Cristina de Oliveira Izar; Andrei Carvalho Spósito; Elizabeth Aparecida Ferraz da Silva Torres
Advisor: Nágila Raquel Teixeira Damasceno

INTRODUCTION: Cardiovascular diseases (CVD) are the leading cause of death worldwide and many of the risk factors are likely to prevention and control. While CVD are complex in their etiology and development, a high concentration of LDL-c and low HDL-c are the most investigated modifiable risk factors in clinical practice, although they are not able to explain all cardiovascular events. So investigate how nutritional and pharmacological interventions can modulate oxidative, physical and structural parameters of lipoproteins can provide additional estimate for cardiovascular risk. Among the many nutrients and bioactive compounds related to CVD, lipids represent the most investigated and described in the literature. In this context, the unsaturated fatty acids (omega-3, omega-6 and omega-9) have been focus of numerous studies. OBJECTIVES: To evaluate the effect of supplementation with omega-3, omega-6 and omega-9 on cardiometabolic parameters in adults with multiple risk factors and without previous cardiovascular event. MATERIAL AND METHODS: Clinical trial, randomized, double-blind, based on nutritional intervention (3.0 g/day of fatty acids) containing: omega-3 (37 per cent EPA and 23 per cent DHA) or omega-6 (65 per cent linoleic acid) or omega-9 (72 per cent of oleic acid). Subjects of both sexes, aged between 30 and 74 years old, with at least one of the following risk factors: hyperlipidemia, diabetes mellitus, obesity and hypertension were included. After Ethics Committee approval, the subjects were distributed on the three intervention groups. At baseline the demographic (gender, age and ethnicity) and clinical (medications, current diseases and family history) data were evaluated. At baseline and after 8 weeks of intervention, blood samples were collected after 12 hours of fasting. From the plasma were analyzed: lipid profile (TC, LDLc, HDL-c, TG), apolipoproteins AI and B, non esterified fatty acid, PON1 activity, LDL (-) and autoantibodies, fatty acids, glucose, insulin, size and distribution of LDL (7 subfractions and phenotype) and HDL (10 subfractions). The effect of time, intervention and associations between fatty acids and qualitative aspects of lipoproteins were evaluated (SPSS version 20.0, p <0.05). RESULTS: A first analysis of the results based on a cross sectional study showed through the linear trend analysis, adjusted by the level of cardiovascular risk, that the highest tertile of plasma DHA was positively associated with HDL-c, HDLLARGE and LDL size and inversely with HDLSMALL and TG. The highest tertile of plasma linoleic acid was positively associated with HDLLARGE and LDL size and negatively with HDLSMALL and TG. This association was not observed when we evaluated the dietary parameters. A sample including smokers supplemented with omega-6 and omega-3 showed that omega-3 positively modify the lipid profile and HDL subfractions. In linear regression models adjusted for age, sex and hypertension, plasma DHA showed negative associations with HDLSMALL. When only assessed the effect of omega-3 in smokers and non-smokers, the results showed that smokers, male, over 60 years old, with low percentage of EPA and DHA (<8 per cent ), overweight and/or obese and high body fat have an increased chance to have HDL subfractions profile less cardioprotective. Based on the above results, we compared the effect of omega-3, omega-6 and omega-9 on cardiometabolic parameters. The omega-3 decreased TG, increase the percentage of HDLLARGE and decrease HDLSMALL. The cardioprotective role of the omega-3 was enhanced by increasing the incorporation of EPA and DHA, in which subjects with more than 8 per cent of EPA and DHA were more likely to have HDLLARGE and lower HDLSMALL. In addition, it was also observed that higher omega-9 plasma levels was associated with less atherogenic LDL particles (phenotype A). CONCLUSION: Plasma fatty acids, but not dietary, correlate with cardiometabolic parameters. Supplementation with omega-3, present in fish oil, promoted reduction in TG and improved the qualitative parameters of HDL (more HDLARGE and less HDLSMALL). The benefits of omega-3 were particularly significant in smokers and those with lower baseline content of EPA and DHA. It was also observed that omega-9, present in olive oil, had a positive impact on the size of LDL. (AU)