N6 and N3 Fatty Acid N6 and N3 Fatty Acid ImbalanceImbalance

Zahra FarazandehZahra Farazandeh

Genetic, Environment, DiseaseGenetic, Environment, Disease11

Genetic factors Genetic factors predispose us to diseasepredispose us to disease

Environment determines Environment determines if genetically if genetically predisposed people are predisposed people are effected by the diseaseeffected by the disease

Nutrition is an Nutrition is an environmental factorenvironmental factor

Genetics influence Genetics influence nutrition and nutrition nutrition and nutrition influences gene influences gene expressionexpression

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Change in DietChange in Diet11

Agriculture – 10,000 years agoAgriculture – 10,000 years ago Dramatically changed the human dietDramatically changed the human diet The modern Western diet changed The modern Western diet changed

dramatically in past 50 yearsdramatically in past 50 years Human DNA rate of change = .5% Human DNA rate of change = .5%

per million yearsper million years Our DNA has not changed to adapt to Our DNA has not changed to adapt to

our dietary changeour dietary change

How?How?

• We are eating more We are eating more saturated fat, trans saturated fat, trans fat, and omega 6 fatty fat, and omega 6 fatty acids, increased acids, increased grains, reduced fruits grains, reduced fruits and vegetablesand vegetables

• We are feeding our We are feeding our animals grainsanimals grains

• The ratio of omega 6 The ratio of omega 6 to omega 3 fatty acids to omega 3 fatty acids changed from 1:1 to changed from 1:1 to 10:1 or even 20:110:1 or even 20:111

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Inflammation!Inflammation!

• Inflammation is part of the bodies defence Inflammation is part of the bodies defence mechanismmechanism

• However, chronic inflammation of blood However, chronic inflammation of blood vessels leads to Atherosclerosisvessels leads to Atherosclerosis

• N6 fatty acids such as arachidonic acid N6 fatty acids such as arachidonic acid induces inflammatory mediators such as induces inflammatory mediators such as prostoglandins, leukotrienes, cytokinesprostoglandins, leukotrienes, cytokines

• DHA and EPA (n3 fatty aicds) down DHA and EPA (n3 fatty aicds) down regulate the effects of n6 fatty acids.regulate the effects of n6 fatty acids.

• The balance is necessary to resolve The balance is necessary to resolve inflammation.inflammation.

ResearchResearch

In vivo studies show decreased In vivo studies show decreased inflammation and atherosclerosis inflammation and atherosclerosis from omega 3 supplementationfrom omega 3 supplementation22

Increased inflammatory markers Increased inflammatory markers from diets high in omega 6 fatty from diets high in omega 6 fatty acidsacids33

Varying N6/N3Varying N6/N344

4 groups of 4 groups of atherosclerosis atherosclerosis genetically susceptible genetically susceptible mice fed varying ratios mice fed varying ratios of N6/N3 fatty of N6/N3 fatty acids: .29,1.43, 5, 8acids: .29,1.43, 5, 8

Group 1 with the lowest Group 1 with the lowest amount of N6 had lower amount of N6 had lower LDL and TG levels, LDL and TG levels, higher HDL levels and higher HDL levels and lowest degree of lowest degree of atherosclerosisatherosclerosis

ResearchResearch

• Some studies did not find any Some studies did not find any significant difference in inflammatory significant difference in inflammatory markers when adding omega 3 markers when adding omega 3 supplementationsupplementation55

• No oxidative damage of DNA in study No oxidative damage of DNA in study supplementing omega 6supplementing omega 666

Reasons for DiscrepanciesReasons for Discrepancies

Amounts of fatty acids supplementedAmounts of fatty acids supplemented Types of damage , if it didn’t show Types of damage , if it didn’t show

DNA damage it doesn’t mean there DNA damage it doesn’t mean there isn’t damage to cell or increased isn’t damage to cell or increased inflammationinflammation

What were the baseline N6/N3 ratios What were the baseline N6/N3 ratios consumed before study?consumed before study?

ConclusionConclusion

Dramatic change in diet such as the N6 and Dramatic change in diet such as the N6 and N3 ratioN3 ratio

Genome has not changed to adaptGenome has not changed to adapt Current nutrition environment affects Current nutrition environment affects

expression of disease such as atherosclerosisexpression of disease such as atherosclerosis Research does show decrease in Research does show decrease in

inflammation and atherosclerosis with not inflammation and atherosclerosis with not only omega 3 supplementation, but only omega 3 supplementation, but correcting the ratio with omega 6 fatty acids correcting the ratio with omega 6 fatty acids as wellas well

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

ReferencesReferences Simopoulos, Artemis PP. Evolutionary Aspects of Diet: The Omega-6/Omega-3 Ratio Simopoulos, Artemis PP. Evolutionary Aspects of Diet: The Omega-6/Omega-3 Ratio

and the Brain". and the Brain". Molecular Neurobiology. Molecular Neurobiology. 2011; 44 (2): 203-215.2011; 44 (2): 203-215. von Schacky, C,von Schacky, C, Angerer P, Kothny W, Theisen K, Mudra H. The effect of dietary The effect of dietary

omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. placebo-controlled trial. Annals of internal medicine. 1999Annals of internal medicine. 1999; 130 (7):554-562.; 130 (7):554-562.

Turpeinen, A M,Turpeinen, A M, Basu S, Mutanen M . A high linoleic acid diet increases oxidative . A high linoleic acid diet increases oxidative stress in vivo and affects nitric oxide metabolism in humans. stress in vivo and affects nitric oxide metabolism in humans. Prostaglandins, Prostaglandins, leukotrienes and essential fatty acids.leukotrienes and essential fatty acids. 1998; 59 (3):229-233. 1998; 59 (3):229-233.

Yamashita, T, Oda E, Sano T, et al. Varying the ratio of dietary nˆ́T’6 nˆ́T’3 Yamashita, T, Oda E, Sano T, et al. Varying the ratio of dietary nˆ́T’6 nˆ́T’3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoEˆ́T’ ˆ́T’ LDLRˆ́T’ ˆ́T’ double knockout mouse. atherosclerosis in apoEˆ́T’ ˆ́T’ LDLRˆ́T’ ˆ́T’ double knockout mouse. Thrombosis researchThrombosis research. . 2005; 116 (5):393-401.2005; 116 (5):393-401.

Petersson H, Rise´rus U*, McMonagle J et al. Effects of dietary fat modification on Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study. oxidative stress and inflammatory markers in the LIPGENE study. British journal of British journal of nutritionnutrition ; 104 (9): 1357-1362. ; 104 (9): 1357-1362.

de Kok TMCM, de Kok TMCM, Zwingmana I, Moonena EJ. Analysis of oxidative DNA damage after Analysis of oxidative DNA damage after human dietary supplementation with linoleic acid. human dietary supplementation with linoleic acid. Food and chemical toxicologyFood and chemical toxicology ; 41 ; 41 (3):351-358(3):351-358