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Artemis P. Simopoulos, M.D.
President
The Center for Genetics, Nutrition and Health
Washington DC, USA
The Importance of the Omega-6/Omega-3
Ratio in Chronic Disease Risk
Functional Forum: The Evolution of Medicine
Arlington, Virginia
October 10, 2016
Effects of PUFA on several genes encoding enzyme proteins
involved in inflammation, adhesion molecules, cell growth, early
gene expression, β-oxidation, and growth factors
Fatty
acid
Cell growth
and early gene
expression
c-fos, Egr-1
Adhesion
molecules
VCAM-1
mRNA**
Inflammation
IL-1B
mRNA
β-oxidation
acyl-CoA
oxidase
mRNA**
Growth
Factors
PDGF
mRNA
LA
LNA
AA
***
EPA
*
DHA
*EPA has no effect by itself but enhances the effect of DHA.
** Monounsaturates also suppress VCAM-1 mRNA, but to a lesser degree than DHA, and induce acyl-CoA oxidase
mRNA
***AA suppresses VCAM-1 mRNA, but to a lesser degree than DHA
suppress or decrease
induce or increase
Simopoulos AP. Annals of Nutrition and Metabolism 1996;40:303-311.
Mechanisms of Omega-6/Omega-3 Fatty Acids
• Linoleic Acid Inhibits Eicosapentaenoic Acid
Incorporation from Dietary Fish Oil Supplements
in Human Subjects
• Linoleic Acid Increases Low-Density Lipoprotein
Oxidation and Severity of Coronary
Atherosclerosis
• As the Omega-6/Omega-3 Ratio Decreases, So
Does the Platelet Aggregation
Mechanisms of Omega-6/Omega-3 Fatty Acids
• Omega-3 Fatty Acids downregulate the
expression of genes involved in inflammation
and obesity
• A Lower Omega-6/Omega-3 Ratio as part of a
Mediterranean Diet Decreases Vascular
Endothelial Growth Factor
• Decreasing Linoleic Acid with Constant αLinolenic Acid in Dietary Fat Increases
Eicosapentaenoic Acid in Plasma Phospholipids
in Healthy Men
ω-6/ω-3 ratio in chronic diseases
In the secondary prevention of
cardiovascular disease, a ratio of 4/1 was
associated with a 70% decrease in total
mortality. A ratio of 2.5/1 reduced rectal
cell proliferation in patients with
colorectal cancer, whereas a ratio of 4/1
with the same amount of omega-3 PUFA
had no effect. The lower omega-6/ omega3 ratio in women with breast cancer was
associated with decreased risk.
ω-6/ω-3 ratio in chronic diseases
A ratio of 2-3/1 suppressed inflammation in
patients with rheumatoid arthritis, and a ratio of
5/1 had a beneficial effect on patients with
asthma, whereas a ratio of 10/1 had adverse
consequences. These studies indicate that the
optimal ratio may vary with the disease under
consideration. This is consistent with the fact
that chronic diseases are multigenic and
multifactorial. Therefore, it is quite possible
that the therapeutic dose of omega-3 fatty acids
will depend on the degree of severity of disease
resulting from the genetic predisposition.
Beneficial Effects of Omega-3 Fatty Acids on Factors
Contributing to Metabolic Syndrome
mega-3 Fatty Acids
Robinson LE et al. Appl Physiol Nutr Metab. 2007 Dec;32(6):1008-24.
A Prospective study of erythrocyte polyunsaturated fatty
acid, weight gain, and risk of becoming overweight or
obese in middle-aged and older women
ω3 and ω6 fatty acids (FA) may have divergent effects on the development
of obesity. The authors examined the association of baseline erythrocyte
ω3 and ω6 FA composition with body weight change and the risk of
becoming overweight or obese in the Women's Health Study (WHS)
participants. They identified 534 women who had baseline erythrocyte FA
measured and a baseline body mass index (BMI) of 18.5-<25 kg/m(2). Body
weight was updated at a total of six time points during follow-up. Weight
gain during a mean of 10.4-year follow-up increased with increasing
quartiles of baseline erythrocyte cis ω6 FA, ω6/ω3 ratio, and trans FA
while decreased with increasing cis ω3 FA.
CONCLUSIONS:
In this prospective study, there is suggestive evidence that erythrocyte cis
ω6 FA may be positively associated, and cis ω3 FA inversely associated
with weight gain in initially normal-weight women.
Wang L et al. Eur J Nutr 2016;55(2):687-97
The effects of dietary EPA and DHA on the composition of the EPA
and DHA in skeletal muscle membrane phospholipids and their
relationship to insulin resistance/hyperinsulinemia and chronic
diseases (obesity, T2DM, hypertension, coronary artery disease)
Simopoulos AP. Nutrients 2013;5(8):2901-23
Conclusions and Recommendations
The importance of omega-3 essential fatty acids in
the diet is now evident, as well as the need to return
to a more physiologic omega-6/omega-3 ratio of
about 1-4/1 rather than the ratio of 20-16/1 provided
by current Western diets. In order to improve the
ratio of omega-6/omega-3 essential fatty acids, it
will be necessary to decrease the intake of omega-6
fatty acids from vegetable oils and to increase the
intake of omega-3 fatty acids by using oils rich in
omega-3 fatty acids and increase the intake of fish
to two to three times per week or take supplements.
Conclusions and Recommendations
Omega-3 fatty acids have been part of our diet since
the beginning of time. It is only for the past 150
years that omega-3 fatty acids have been decreased
in Western diets due to agribusiness and food
processing. The need to return the omega-3 fatty
acids into the food supply has been recognized by
industry, which is already producing omega-3
enriched products.
Conclusions and Recommendations
Because chronic diseases are multigenic
and multifactorial it is essential in designing
clinical trials that the background diet, the
omega-6/omega-3 ratio and the genetic
variants are taken into consideration.
Adequate intakes (AI) for adults
Fatty Acid
Grams/day (2000 kcal diet)
% Energy
LA
4.44
2.0
(Upper Limit)1
6.67
3.0
LNA
2.22
1.0
DHA + EPA
0.65
0.3
DHA to be at least2
0.22
0.1
EPA to be at least
0.22
0.1
2.00
1.0
(Upper limit)4
--
< 8.0
MONOs5
--
--
TRANS-FA
(Upper limit)3
SAT
1. Although the recommendation is for AI, the Working Group felt that there is enough scientific evidence to also state an upper
limit (UL) for LA of 6.67 g/d based on a 2000kcal diet or of 3.0% of energy.
2. For pregnant and lactating women, ensure 300 mg/d of DHA.
3.Except for dairy products, other foods under natural conditions do not contain trans-FA. Therefore, the Working Group does
not recommend trans-FA to be in the food supply as a result of hydrogenation of unsaturated fatty acids or high temperature
cooking (reused frying oils).
4.Saturated fats should not comprise more than 8% of energy.
5. The Working Group recommended that the majority of fatty acids are obtained from monounsaturates. The total amount of fat
in the diet is determined by the culture and dietary habits of people around the world (total fat ranges from 15-40% of energy)
but with special attention to the importance of weight control and the reduction of obesity.
Simopoulos AP , Leaf A, Salem N Jr, J Am Coll Nutr 1999;18(5):487-9