As far as I can tell, some sort of stimuli, whether it be an injury or just a need to constrict or dilate something causes various phospholipases to hack a fatty acid out of the membrane of a cell for conversion into an eicosanoid. These phospholipases have very specific tasks that they are sent out to accomplish:
Those are the actions of 4 different ones. When that fatty acid is released it can then become the corresponding signalling molecule. The only way that I can see for the system to break down is if there is a dietary deficiency in either the n-3 or n-6 fats that would make it difficult for these phospholipases to find their targets. Assuming that you met the minimums for these fats (whatever they may be), the signalling would proceed as designed.
According to S. Guyenet, the amounts of both of these have increased in the American diet (with much more being n-6 of course). This would indicate that a deficiency has probably not worsened.
If you look at this:
Grain-fed beef has less n-6 fats than wild game. I'm not saying this is anything near the SAD, just that the real difference appears to be less n-3. Indeed, the seasonal consumption of nuts could skew this temporarily. If hunter-gather's have to eat a high n-6 fat diet temporarily, do they experience more inflammation during that period?
The "n-6 fats cause inflammation" idea implies that all of it is instantly converted into inflammation signalling molecules as it is digested, but really, they're just getting packed into fat cells or oxidized in mitochondria like any other fat until they are called upon to be converted. The composition of our diets is reflected in the fatty acid composition of our depot fat, but to say that a particular fatty acid stored in an adipocyte is more or less inflammatory than another is baseless, as far as I can tell.
To be clear, I'm not saying that industrial seed oils are healthy by any means. I think they are unhealthy because of possible oxidation/rancidity and because their chain lengths could make them more conducive to lipogenesis. I just don't see how a particular tribe focusing on bison and brains is going to have less inflammation than one focusing on elk + nuts. It simply doesn't make sense provided that they both hit the minimums.
It seems to me that a greater risk is in a deficiency of either one, or in a less than optimal starting point for synthesis (i.e. linoleic acid instead of arachidonic acid) but if you ate enough arachidonic acid, maybe that there is so much more linoleic acid wouldn't matter. I'm assuming that cell membranes would be constructed of the optimal components if enough of them are consumed, even if less optimal components are consumed as well.
I haven't really thought about this before, so if I'm missing something let me know.
You're right that it isn't just omega-6 = more eicosanoids = more inflammation, it's not linear and levels out, and in fact we want a little more than that because we need those eicosanoids. You are also right that a deficiency in omega-3 fats is behind the obscene excessive inflammation that causes disease. The ability to signal "off" or protect the body is the most important factor. There are other factors, and certainly the increased need for the immune system plays a role. An infection or a gluten allery would do it, so would anything that incites the immune system to a degree. This is unwanted inflammation, but isn't caused by omega-6.
But high-dose omega-6 is not innocous, since it causes a DHA deficiency. Excess omega-6 impairs ALA conversion, and it competes for space in cellular phospholipids with DHA. There is a scientist named Bill Lands who talks about this a lot. Stephan has also written about it. So mega doses of omega-6 certainly aren't off the hook. They are anti-anti-inflammatory in the most important sense. You might see short-term benefit via certain mechanisms, but the effect is a J curve (http://healthcorrelator.blogspot.com/2011/09/nonlinearity-and-industrial-seed-oils.html), if you want the best of the best inflammatory signaling you want to keep omega-6 below 4% of calories so that it doesn't cause an omega-3 deficiency. And of course you want more omega-3.
This should explain many paradoxes. It's really all about the "omega-3 index", the available omega-3 in the cells to do anti-inflammatory heavy-lifting. If two groups have similarly poor omega-3 intake (like 95% of rat studies) then you will likely not see a difference, or you might even see a higher omega-6 group do better due to GLA and DGLA, possibly. But if you have a fixed amount of omega-3 across all groups and an obscene amount of omega-6 in one of them, the omega-6 group will be worse because the omega-3 index will be lower due to the omega-6 in the diet. The only desirable diet is one that has a reasonable amount of omega-6 and sufficient omega-3, change either variable and you're headed downhill. Studies that demonstrate that halfway down the hill is better than all the way down the hill lying on some broken bottles with a twisted ankle do nothing to help us, and waste lab rats.
Dietary ratio is a useful tool and is predictive, but it isn't air-tight. Cellular ratio is better and predicts many diseases. http://omega-6-omega-3-balance.omegaoptimize.com/
Stephan seems to think so:
Honestly, the basis for saying that n-6 causes inflammation is mostly hypothetical. I've come to realize that the case based on eicosanoid formation has been overstated. The strongest piece of evidence is that excess n-6 seems to suppress n-3 elongation and accumulation, and we know that n-3 is important in resolving inflammation....
I think Dr. Willett is correct that the evidence has been exaggerated that higher LA will lead to higher production of inflammatory eicosanoids. At least above a certain threshold, it doesn't seem to matter much.I'm also reminded of this:
In a 1993 trial, a low-magnesium diet reduced insulin sensitivity in healthy volunteers by 25% in just four weeks (8). It also increased urinary thromboxane concentration, a potential concern for cardiovascular health**.
More omega 6 over 3 does cause inflammation.
Try an experiment: Eat oatmeal that is HIGH in 6, and watch your inflammation spike.