I was recently asked for evidence beyond blogs or opinion pieces on the problems with omega 3/6 ratios and how important they are. I have read that o3 isn't all that important and supplementing is unnecessary. I have searched Pubmed but nothing helpful came up. Has anybody any evidence for the inflammatory harm of omega 6 (again not blog posts unless backed by peer-reviewed studies) and the importance of the 3/6 ratio of 1:1 so often quoted?
The data suggest that the most important aspect of PUFA in the prevention of mammary cancer is the ratio of (n-3) to (n-6) PUFA rather than the absolute concentration of either. Research indicates that a ratio of ∼1:1–1:2 has the most protective effect against the development and growth of mammary cancers. If this is indeed the case, a closer look at human and animal diets, whose (n-3)-to-(n-6) average ratio is considerably higher (∼1:20 and 1:10, respectively) (8 ,43) , may be warranted.
Human trials confirmed that LC n-3 PUFA from either fish or fish oil supplements as well as ALA enrichment significantly reduce blood triglyceride levels in patients with MetS in a dose-dependent manner [35, 68], an effect that appears to be mediated through inhibition of hormone-sensitive lipase and VLDL secretion, and increase in apo B liver degradation .
A body of evidence demonstrates that n-3 PUFA are involved in the control of glucose homeostasis and insulin sensitivity . In murine models of obesity and insulin resistance, incorporation of LC n-3 PUFA into cell membrane phospholipids increases membrane fluidity and expression, affinity, and number of insulin receptors  as well as GLUT-4 protein level in adipocytes , thereby improving insulin sensitivity. In overweight patients, n-3 PUFA reduce transition from glucose intolerance to T2DM , and fish and fish oil consumption during energy reduction elicit an additional positive effects on insulin resistance . However, a majority of n-3 PUFA administration trials did not prove efficient in reducing insulin resistance in T2DM .
Diet interventions with increased n-3 PUFA clearly demonstrated therapeutically, reliability in lowering mortality in subjects with cardiovascular diseases or the MetS [31, 72], an effect primarily related to increased DHA intakes . This justifies the recommendation for daily consumption of 1g/d of LC n-3 PUFA as part of secondary prevention strategy post ischemic heart event .
NAFLD, now recognized as the hepatic complication of the MetS, might trigger development of T2DM. Low dietary n-3 PUFA content induces hepatic desaturase activity . In addition, enzymes involved in eicosanoid synthesis are located at the periphery of lipid droplets . It is therefore plausible that in the context of diet- or obesity-induced fatty liver associated with excessive n-6/n-3 ratio, hepatic eicosanoid production is tilted towards proinflammatory components and participates to proinflammatory and insulin resistant status aggravating the MetS. Animal diet-induced obesity experiments clearly show that EPA and DHA supplementation reduces severity of NAFLD, if not preventing it , suggesting that increasing n-3 PUFA intake and fish consumption might prevent the occurrence of NAFLD in humans . Properly conducted clinical trials are awaited to confirm this.
As important, emerging evidence indicates that incidence and tumour growth of some cancers associated with the MetS can be attenuated by n-3 PUFA . Independently of the total amount of n-3 PUFA, the n-6/n-3 ratio seems to be determinant as 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 n-3 PUFA had no effect .
1:1 is often quoted but 2:1 or 3:1 seems more realistic and just as healthy
Here are a few other articles
Recommendations to increase omega-6 intake are misguided, omega-6 specific interventions tend to increase CHD risk, and the substitution of n-6 PUFA for TFA and SFA produced an increased risk of death from all causes that approached statistical significance when analyzed independently or in comparison to mixed n-3/n-6 PUFA diets.
Exposure to high omega-6 diets over multiple generations showed increases in both size and number of fat cells contained within each generation, as well as increased insulin resistance
Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn’s disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB4 produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo- controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.