1. N6 and N3 Fatty Acid Imbalance Zahra Farazandeh

2. Genetic, Environment, Disease 1 Genetic factors predispose us to disease Genetic factors predispose us to disease Environment determines if genetically predisposed people are effected by the disease Environment determines if genetically predisposed people are effected by the disease Nutrition is an environmental factor Nutrition is an environmental factor Genetics influence nutrition and nutrition influences gene expression Genetics influence nutrition and nutrition influences gene expression library.think quest.org

3. Change in Diet 1 Agriculture – 10,000 years ago Agriculture – 10,000 years ago Dramatically changed the human diet Dramatically changed the human diet The modern Western diet changed dramatically in past 50 years The modern Western diet changed dramatically in past 50 years Human DNA rate of change =.5% per million years Human DNA rate of change =.5% per million years Our DNA has not changed to adapt to our dietary change Our DNA has not changed to adapt to our dietary change

4. How? We are eating more saturated fat, trans fat, and omega 6 fatty acids, increased grains, reduced fruits and vegetables We are eating more saturated fat, trans fat, and omega 6 fatty acids, increased grains, reduced fruits and vegetables We are feeding our animals grains We are feeding our animals grains The ratio of omega 6 to omega 3 fatty acids changed from 1:1 to 10:1 or even 20:1 1 The ratio of omega 6 to omega 3 fatty acids changed from 1:1 to 10:1 or even 20:1 1 http://2.bp.blogspot.com/_qdPXC- 9Mgp4/Sm_FfpGWUtI/AAAAAAAACkQ/ghazZ5pYwRI /s400/vegetable+oil.jpg

5. Inflammation! Inflammation is part of the bodies defence mechanism Inflammation is part of the bodies defence mechanism However, chronic inflammation of blood vessels leads to Atherosclerosis However, chronic inflammation of blood vessels leads to Atherosclerosis N6 fatty acids such as arachidonic acid induces inflammatory mediators such as prostoglandins, leukotrienes, cytokines N6 fatty acids such as arachidonic acid induces inflammatory mediators such as prostoglandins, leukotrienes, cytokines DHA and EPA (n3 fatty aicds) down regulate the effects of n6 fatty acids. DHA and EPA (n3 fatty aicds) down regulate the effects of n6 fatty acids. The balance is necessary to resolve inflammation. The balance is necessary to resolve inflammation.

6. Research In vivo studies show decreased inflammation and atherosclerosis from omega 3 supplementation 2 In vivo studies show decreased inflammation and atherosclerosis from omega 3 supplementation 2 Increased inflammatory markers from diets high in omega 6 fatty acids 3 Increased inflammatory markers from diets high in omega 6 fatty acids 3

7. Varying N6/N3 4 4 groups of atherosclerosis genetically susceptible mice fed varying ratios of N6/N3 fatty acids:.29,1.43, 5, 8 4 groups of atherosclerosis genetically susceptible mice fed varying ratios of N6/N3 fatty acids:.29,1.43, 5, 8 Group 1 with the lowest amount of N6 had lower LDL and TG levels, higher HDL levels and lowest degree of atherosclerosis Group 1 with the lowest amount of N6 had lower LDL and TG levels, higher HDL levels and lowest degree of atherosclerosis

8. Research Some studies did not find any significant difference in inflammatory markers when adding omega 3 supplementation 5 Some studies did not find any significant difference in inflammatory markers when adding omega 3 supplementation 5 No oxidative damage of DNA in study supplementing omega 6 6 No oxidative damage of DNA in study supplementing omega 6 6

9. Reasons for Discrepancies Amounts of fatty acids supplemented Amounts of fatty acids supplemented Types of damage, if it didn’t show DNA damage it doesn’t mean there isn’t damage to cell or increased inflammation Types of damage, if it didn’t show DNA damage it doesn’t mean there isn’t damage to cell or increased inflammation What were the baseline N6/N3 ratios consumed before study? What were the baseline N6/N3 ratios consumed before study?

10. Conclusion Dramatic change in diet such as the N6 and N3 ratio Dramatic change in diet such as the N6 and N3 ratio Genome has not changed to adapt Genome has not changed to adapt Current nutrition environment affects expression of disease such as atherosclerosis Current nutrition environment affects expression of disease such as atherosclerosis Research does show decrease in inflammation and atherosclerosis with not only omega 3 supplementation, but correcting the ratio with omega 6 fatty acids as well Research does show decrease in inflammation and atherosclerosis with not only omega 3 supplementation, but correcting the ratio with omega 6 fatty acids as well

11. How can we vary take control of our dietary fat balance? How can we vary take control of our dietary fat balance?

12. References Simopoulos, Artemis PP. Evolutionary Aspects of Diet: The Omega-6/Omega-3 Ratio and the Brain". Molecular Neurobiology. 2011; 44 (2): 203-215. Simopoulos, Artemis PP. Evolutionary Aspects of Diet: The Omega-6/Omega-3 Ratio and the Brain". Molecular Neurobiology. 2011; 44 (2): 203-215. von Schacky, C,The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Annals of internal medicine. 1999; 130 (7):554-562. von Schacky, C, Angerer P, Kothny W, Theisen K, Mudra H. The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Annals of internal medicine. 1999; 130 (7):554-562. Turpeinen, A M,. A high linoleic acid diet increases oxidative stress in vivo and affects nitric oxide metabolism in humans. Prostaglandins, leukotrienes and essential fatty acids. 1998; 59 (3):229-233. Turpeinen, A M, Basu S, Mutanen M. A high linoleic acid diet increases oxidative stress in vivo and affects nitric oxide metabolism in humans. Prostaglandins, leukotrienes and essential fatty acids. 1998; 59 (3):229-233. Yamashita, T, Oda E, Sano T, et al. Varying the ratio of dietary nˆ́’6 nˆ́’3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoEˆ́’ ˆ́’ LDLRˆ́’ ˆ́’ double knockout mouse. Thrombosis research. 2005; 116 (5):393-401. Yamashita, T, Oda E, Sano T, et al. Varying the ratio of dietary nˆ́’6 nˆ́’3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoEˆ́’ ˆ́’ LDLRˆ́’ ˆ́’ double knockout mouse. Thrombosis research. 2005; 116 (5):393-401. Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study. British journal of nutrition ; 104 (9): 1357-1362. Petersson H, Rise´rus U*, McMonagle J et al. Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study. British journal of nutrition ; 104 (9): 1357-1362. de Kok TMCM, Analysis of oxidative DNA damage after human dietary supplementation with linoleic acid. Food and chemical toxicology ; 41 (3):351-358 de Kok TMCM, Zwingmana I, Moonena EJ. Analysis of oxidative DNA damage after human dietary supplementation with linoleic acid. Food and chemical toxicology ; 41 (3):351-358