The emerging picture on n-6 is that adequate intake is somewhere between 0.5% and 1% of calories with toxicity developing somewhere between 3% and 10% of calories depending on the amount of n-3 stored in the tissue. 
The catch is n-3 is even more volatile than n-6, making safe forms of n-3 supplementation hard to find and placing limits on the amount of supplementation which can be safely consumed. 

The 2015 “Scientific” Report of the Dietary Guidelines Advisory Committee recommended Vegetable Oil as the primary fat despite the fact estimated US consumption of n-6 PUFA is at 9% (probably a low estimate) and 10% is the high end for tolerance (and probably a high estimate). 

There are identified mechanisms tying PUFA excess to cardiovascular disease, liver disease and obesity. These are strong ties (it will happen) not loose ties (it may happen). The only question is at what level and predictions for heart disease tie closely with observations. There are well documented increases in all three diseases since vegetable oil consumption increased. 
Bill Lands: 2014 Review of EFA

Historical perspectives on n-3 & n-6 impact to health.

Healthy intake levels of n-3 & n-6

n-6 involvement in the development of cardiovascular disease.

n-6 and overeating in the development of cardiovascular disease.

Issues with dietary recommendations  
Nutritionists View on n-6/n-3

Outstanding information on the hazards of PUFA perioxidation. 

Followed by perplexing recommendations of mitigating the hazards with anti-oxidant supplementation and n-3 (which is even more volatile than n-6) supplementation. 

The Slow Discovery of Essential Fatty Acids

Details on the original meaning of “essential” when it comes to n-3 & n-6 (necessary for growth rate and skin quality in mice) and details on how hard it is to develop a PUFA deficiency (answer: damage the intestines and place on a zero fat intravenous diet).
Out of Balance You Tube Video

Promotional video by a company selling seafood Seafood bias but well produced and some good info. 

Links between PUFA excess and impact to mental health.

Ties in to the report which came out this week on a rise in death rate for middle age white males. 

Impact to mental health back in 1972.

The Issue:
DGAC: Dietary Guidelines Advisory Committee 

PUFA: Polyunsaturated Fatty Acid

SFA: Saturated Fatty Acid

Every five years a Dietary Guidelines Advisory Committee (DGAC) is formed to review US dietary guidelines. The most recent DGAC released it’s 2015 Scientific Report in February.

The 2015 DGAC report recommends Americans use vegetable oil as their primary source of fat. Here’s the wording from the report:

“In practice, non-hydrogenated vegetable oils that are high in unsaturated fats and relatively low in SFA (e.g., soybean, corn, olive, and canola oils) instead of animal fats (e.g., butter, cream, beef tallow, and lard) or tropical oils (e.g., palm, palm kernel, and coconut oils) should be recommended as the primary source of dietary fat.”

The 2015 recommendation is a more extreme continuation of a recommendation developed in the 1970’s to avoid saturated fat. Americans have heeded the recommendation to avoid saturated fat but relied primarily on carbohydrates as a substitute. The 2015 report found that the shift from saturated fat to carbs adversely affects health and therefore recommends emphasizing polyunsaturated fatty acids (PUFAs) as a replacement for saturated fat. The 2015 report acknowledges there are no studies which show a link between saturated fat consumption and cardiovascular disease.

There are three significant concerns with the 2015 DGAC recommendation:

1) The recommendation is based on statistical analysis of imprecise data and predictions based on computer models. The predictions ignore chemistry.

2) The recommendation is based on an assumption that lowering low density lipoprotein levels by increasing PUFA consumption will reduce the risk of cardiovascular disease. It will not reduce the risk. There is strong evidence it will increase the risk of, not only cardiovascular disease, but also obesity and liver disease.
3) The DGAC recommends replacing a chemically stable substance which has been consumed for millions of years (saturated fat from plants and animals) with chemically unstable manufactured substances (soybean, corn, olive, and canola oils).

The debate over fat is not new. 

Gary Taubes and Nina Teicholz have both published well researched accounts of the gaps in the evidence supporting U.S. dietary recommendations on fat. 

Credit Suisse Research Institute also released a report on dietary fat this year. Although the report is not perfect, it provides a good overview of the evidence against consumption of excess PUFA.

The report can be found here: http://bit.ly/1KwjnFD

Discussion of the Credit Suisse report appears to have been limited to nutrition and financial circles. The general public is effectively numb to any new cries of wolf even though this one is legitimate.

The conflicting evidence should at least give the DGAC pause. It has not. 

In a quote listed in a September 2015 British Medical Journal article, Barbara Millen, the DGAC Chairman, was quoted as saying “we thought we nailed it” regarding the recommendation on saturated fat. When Nina Teicholz asked Alice Lichtenstein, the DGAC Vice Chairman, about the evidence related to low density lipoproteins and heart disease, Lichtenstein replied that it was “complicated” and she “didn’t have time to review it.”

From Bill Lands:

Historical perspectives on the impact of n-3 and n-6 on health

A likely candidate for a very early step in atherogenesis is the repeated postprandial reversible loss of endothelial function [55] and [56] which could occasionally convert into a chronic inflammatory locus. Endothelium-dependent dilation is lower with higher postprandial triacylglycerolemia (a marker for high food energy density). An often-neglected postprandial process when excess food energy forms the much-discussed circulating blood biomarker low-density lipoprotein (LDL) is the hydrolytic release of large amounts of non-esterified fatty acid (NEFA) into the plasma [10]. The biological impact of the much-neglected NEFA and its resultant oxidant stress (indicated in Fig. 3B) may be greater than the effect of the co-produced LDL (with its adherent cholesterol). However, daily messages about LDL cholesterol from marketing and research groups greatly exceed information on the simultaneously released NEFA, and they divert attention away from harmful NEFA actions.

8.1 Actions of non-esterified fatty acids (NEFA) amplified by n-6 mediators

Meal-induced vascular dysfunction and oxidative inflammatory conditions (measured by hydrogen peroxide and isoprostane levels) as well as released monocyte chemoattractant protein-1 were less when diets included fish oil n-3 HUFA [57]. Lipemia-induced loss of endothelial function involves impaired nitric oxide actions, and it can be alleviated in part by supplements of arginine [58]. However, arginine did not prevent an accompanying pro-thrombotic expression of P-selectin and vonWillebrand factor on platelets. Impaired endothelial function monitored as flow-mediated dilation after an oral fat challenge was related to the extent of hypertriacylglycerolemia and oxygen-derived free radicals [59]. Postprandial lipemia was accompanied by increased plasma hydroperoxides and a neutrophil chemotactic agent, IL-8 [60].

Importantly, leukocyte chemotaxis and adhesion are much greater when the mediator is n-6 LTB4 rather than n-3 LTB5 [54]. A significant increase in adhesion of monocytes to the endothelial monolayer occurred in the presence 20:4n-6, and it was decreased with 20:5n-3 [61]. Pro-inflammatory mediators (intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-Selectin, IL-6, and TNFα) were all significantly increased in endothelial cells incubated with 20:4n-6. Thus, the n-3 and n-6 HUFA proportions in tissues shown in Fig. 3A must be considered when interpreting the impact of food energy density upon risk for CVD shown in Fig. 3B.

Important arithmetic in managing food energy is in balancing intake with expenditure during the course of a day. The on-going societal shift toward a sedentary lifestyle puts a premium on awareness of energy intake and expenditure. During 3 h of typical modern lifestyle activities, a 150 lb person may expend approximately: 225 Cal riding in a car; 202 Cal using computer/internet; 216 Cal watching television; 202 Cal reading book/newspaper; 202 Cal sleeping. Physical activity like walking for 1 h may expend about 270 Cal, and one hour of bicycling, about 500 Cal.

In contrast to low energy expenditure, an average restaurant meal may have 1327 Cal [62], which is 1100 in excess of that likely to be burned in the next 3 h. As a result, much remains for the liver to convert to plasma VLDL and begin the transient process of postprandial endothelial dysfunction. An important, simple tactic to distribute food energy intake more evenly is to eat fewer calories per meal and use small snacks to lower the burden of food energy per hour upon the liver.

With three meals per day and 365 days per year, people may have a thousand postprandial situations per year. If only one per hundred (1%) of these transient postprandial insults converted to a chronic inflammatory site, there might be 10 new sites each year leading to 200 sites in 20 year-old individuals, 400 in 40-year olds and 600 in 60-year olds. Such a low frequency for initiation fits the slow age-dependent histological evidence in the PDAY Study (see Fig. 14 in [10]). While food energy can give reversible pathologies, a more serious process may be the n-6 mediated amplification of transient dysfunction into chronic inflammatory plaques.

The propensity for recruiting macrophages that convert a vascular area into a chronic inflammatory site is much greater when the tissue HUFA balance has a high %n-6 in HUFA. In this way, the higher risk of mortality associated with higher levels of the food energy biomarker, cholesterol (Fig. 1), is seen in populations that have a higher HRA value for the %n-6 in HUFA. A high prevalence of CVD for Americans has remained for decades near 40% for 40-year olds, 60% for 60-year olds and 80% for 80-year olds [63] indicating a failure to prevent the continual disease progression that the PDAY Study showed to begin youth.

Fig. 3A shows how n-3 and n-6 mediators act in CVD, and Fig. 3B shows how food energy intake leads to a high body mass index (BMI) or obesity, which is a predictive associated risk factor for CVD. While factors that cause obesity may also cause CVD, a high BMI per se is not a certain cause of vascular damage, CVD or death. A very large expensive effort to lower CVD by lowering BMI with intensive lifestyle intervention of 5145 overweight or obese patients in 16 study centers [64] gave weight loss through decreased caloric intake and increased physical activity. However, the trial was stopped after millions of dollars and 9.6 years of follow-up showed no lowering of observed risk of cardiovascular morbidity or mortality compared with controls. While many people believe that obesity (high BMI) causes death, the fatal mechanisms and mediators will need to be better identified and prevented if we are to design cost-effective interventions that prevent harm from food energy.