Nutrients Journal Received: 15 January 2016; Accepted: 15 February 2016; Published: 2 March 2016
Artemis P. Simopoulos, The Center for Genetics, Nutrition and Health, 4330 Klingle Street NW, Washington, DC 20016, USA; cgnh at bellatlantic.net
In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation.
Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.
Table 4. Omega-6/Omega-3 Ratios in Different Populations.
|Greece prior to 1960||1.00-2.00|
|Current India, rural||5-6.1|
|Current UK and northern Europe||15.00|
|Current India, urban||38-50|
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- Human beings evolved on a diet that was balanced in the omega-6 and omega-3 essential fatty acids.
- A high omega-6 fatty acid intake and a high omega-6/omega-3 ratio are associated with weight gain in both animal and human studies, whereas a high omega-3 fatty acid intake decreases the risk for weight gain. Lowering the LA/ALA ratio in animals prevents overweight and obesity.
- Omega-6/omega-3 fatty acids compete for their biosynthetic enzymes and because they have distinct physiological and metabolic properties, their balanced omega-6/omega-3 ratio is a critical factor for health throughout the life cycle.
- Adipose tissue is the main peripheral target organ handling fatty acids, and AA is required for adipocyte differentiation (adipogenesis). The increased LA and AA content of foods has been accompanied by a significant increase in the AA/EPA + DHA ratio within adipose tissue, leading to increased production in AA metabolites, PGI2 which stimulates white adipogenesis and PGF2a which inhibits the browning process, whereas increased consumption of EPA and DHA leads to adipose tissue homeostasis through adipose tissue loss and increased mitochondrial biogenesis.
- High omega-6 fatty acid intake leads to hyperactivity of endocannabinoid system, whereas omega-3 fatty acids lead to normal homeostasis (decrease hyperactivity).
- High omega-6 fatty acids increase leptin resistance and insulin resistance, whereas omega-3 fatty acids lead to homeostasis and weight loss.
- Because a high omega-6/omega-3 ratio is associated with overweight/obesity, whereas a balanced ratio decreases obesity and weight gain, it is essential that every effort is made to decrease the omega-6 fatty acids in the diet, while increasing the omega-3 fatty acid intake. This can be accomplished by (1) changing dietary vegetable oils high in omega-6 fatty acids (corn oil, sunflower, safflower, cottonseed, and soybean oils) to oils high in omega-3s (flax, perilla, chia, rapeseed), and high in monounsaturated oils such as olive oil, macadamia nut oil, hazelnut oil, or the new high monounsaturated sunflower oil; and (2) increasing fish intake to 2-3 times per week, while decreasing meat intake.
- In clinical investigations and intervention trials it is essential that the background diet is precisely defined in terms of the omega-6 and omega-3 fatty acid content. Because the final concentrations of omega-6 and omega-3 fatty acids are determined by both dietary intake and endogenous metabolism, it is essential that in all clinical investigations and intervention trials the omega-6 and omega-3 fatty acids are precisely determined in the red blood cell membrane phospholipids. In severe obesity drugs and bariatric surgery have been part of treatment.
- The risk allele rs 1421085 T to C SNV in intron 1 and 2 in the FTO gene functioned similarly to AA metabolites, PGI2 and PGF2a increasing proliferation of white adipose tissue and decreasing its browning respectively, whereas the knockdown of IRX3 and IRX5 genes functioned similarly to omega-3 fatty acid metabolites increasing the browning of white adipose tissue, mitochondrial biogenesis, and thermogenesis. Therefore, further research should include studies on the effects of omega-3 fatty acids in blocking the effects of the risk allele (rs 1421085), which appears to be responsible for the association between the first intron of FTO gene and obesity in humans.
- In the future studies on genetic variants from GWAS will provide opportunities to precisely treat and prevent obesity by both nutritional and pharmaceutical interventions.
Obesity is a preventable disease that can be treated through proper diet and exercise.
A balanced omega-6/omega-3 ratio 1-2/1 is one of the most important dietary factors in the prevention of obesity, along with physical activity.
A lower omega-6/omega-3 ratio should be considered in the management of obesity.