Linoleic Acid: Is This The Key That Unlocks The Quantum Brain?

haidut

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Corn oil is actually worse because it has much more linoleic acid, the only precursor to the prostaglandins.

The old studies on high‐fat diets in rats, dating back to the '40s, had shown a high fat diet to promote cancer. Later on, in the '70s, it had been shown that some fats were far more carcinogenic than others. The most carcinogenic fatty acid was always corn oil.

And then later, in the '80s, review articles from all these fat‐feeding rat studies had teased‐out one important finding: linoleic acid content! While it's common to separate fatty acids into two groups, saturated and unsaturated, this is a simplification which hides important details. Only arachidonic acid can become prostaglandins, and arachidonic acid is exclusively made from linoleic acid. When arachidonic acid is concentrated on the cell membrane, you have potential for 'inflammation' and cancer.

The enzyme phospholipase A₂ cleaves arachidonic acid from a phospholipid on the cell membrane. This is a cool enzyme, and it can do this in vitro. This enzyme can be shown to work using simple micelles—or artificial lipid droplets in water—constructed of phosphotidylcholine, with arachidonic acid at the sn‐2 position or course. This enzyme has an affinity for the lipid membrane and can catalyze the cleavage of the arachidonic acid–phospholipid bond.

Released arachidonic acid then diffuses towards cyclooxygenase, which adds O₂ to the lipid forming the endoperoxide ring characteristic of prostaglandin H. This is then isomerized to either prostaglandin D₂ or prostaglandin E₂. These have opposing functions, to a degree, as prostaglandin D₂ usually constricts the blood vessels while prostaglandin E₂ always relaxes them.

But they have hormonal functions to, besides those mediated through their G protein‐coupled receptors on microtubules. The PPAR series of nuclear receptors can bind prostaglandins, and then induce transcription of enzymes and proteins.

But there is another twist, since the entire process can be mitigated by competing fatty acids. Oleic and eicosapentaenoic acids have been shown to inhibit prostaglandin production by: (1) Displacing it from the cell membrane, and (2) Competing with it for the cyclooxygenase enzyme. This is why ω−3 fatty acids are considered 'protective.'

But omega−3 fatty acids cannot be said to be 'protective' against spontaneous oxidation or lipofuscin. In fact, some of them are even more prone to oxidation since they can have upwards of six double‐bonds. So between corn oil and fish oil you are presented with a dilemma: Either you can have the growth promoting, proliferative, and carcinogenic corn oil . . . or you can have the more unstable yet relatively non‐proliferative fish oil. If a person had cancer, they'd probably have to choose the fish oil; but if a person was underweight and taking iron supplements for some reason, the more stable corn oil could be a better choice.

But I would think the IQ point difference could have been influenced more by the vitamins in the fish oil. This oil is naturally rich in vitamin A, but it also has significant amounts of vitamin D. However, it is often deodorized—a process which largely removes these vitamins. Sometimes they are added back in, but the concentrations are always somewhat unnatural (vitamin A‐heavy). Vitamin A is powerful lipid hormone which can effect nearly everything. Active vitamin A, or retinoic acid, has two nuclear receptors which double as transcription factors. Upon binding retinoic acid, these receptors cumulatively transcribe DNA for thousands of genes.

It would be nice to see a study controlling for vitamin A, also having a coconut oil group.

Actually, a much more recent study kept calling corn oil a known "tumor promoter" and used glycine to block its effects. So, apparently in some scientific circles the truth is well-known.
PUFA are carcinogenic, dietary glycine blocks their effect
 

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Travis

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Mito

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But there is another twist, since the entire process can be mitigated by competing fatty acids.
Is there a ratio of competing fatty acids to linoleic acid in the diet that could theoretically mitigate the negative effects of linoleic acid? For example if I average eating 50 grams of competing fatty acids (like stearic, palmitic and oleic) but I also average eating 5 grams of linoleic acid per day, is that a high enough ratio to significantly inhibit prostaglandin production?
 

haidut

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...I wonder what 100% linoleic acid would do?

I think I saw a study on that. Very few of them done, for obvious reasons. I will try to find and post here but from I remember, it shortened lifespan by 60% in rats.
 
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Travis

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I think I saw a study on that. Very few of them done, for obvious reasons. I will try to find and post here but from I remember, it shortened lifespan by 60% in rats.
That is insane, but not too surprising. I would image those to have been very chubby rats.

And it looks as if I was right about the lipofuscin. Check out these rate constants of autooxidation with increasing double bonds:

autooxidation.png


Anyone could have guessed this, of course, but here are the numbers. These rates weren't entirely spontaneous, as the peroxidation was started with an initiator (column 1).

So although linoleic acid indisputably has the most hormonal potential, it's ability to catalyze lipofuscin formation is relatively mild compared to the fish oils. I wonder if how many 'age spots' you see in the Norwegians, or if they have ever actually compared lipofuscin via microscope between two or more populations.

Between the double bonds of linoleic acid is a bis‐allylic hydrogen, which is relatively more acidic than all the rest; the removal of this hydrogen takes less energy than any other (291⋅kJ/mol). The loss of H⋅ forms a free radical, onto which O₂ is then added:

linoleic acid.png


Oleic acid, with only one double bond, will not react with the hydrodioxyl radical (⋅O–OH). I think it's safe to consider olive oil as the #2 oil—behind coconut and perhaps macadamia oil—although it will oxidize with heat (thousands of cooking utensils will attest to this fact.)

'Thermodynamically, the hydrodioxyl radical should also be able to oxidize the singly allylic hydrogen in oleic acid, but no evidence for this reaction has been found [15].' ―Kopperol

'While linoleic, linolenic, and arachidonic acids react with HO₂, oleic and a mixture of 9,11- and 10,12-octadecadienoic acids do not, thereby suggesting that double allylic H atoms are required for Reaction 1 to occur.' ―Benon

So the best general inhibitor of cyclooxygenase is probably just aspirin and oleic acid, while both stearic and oleic acids can displace linoleic and arachidonic acid esters from the cell membrane. It seems as if we'd evolved on a low‐linoleate diet, and now modern foods are creating noise in the elaborate lipid hormone system we had evolved under.

Lipofuscin is formed from the addition of another O₂ to the unsaturated fatty acid, followed by a bond cleavage:

linoleic acid2.png


And these reactive aldehydes are what crosslink proteins (at lysine, histidine, and arginine side‐chains mostly).

crosslink.png


Brunk and Terman will tell you that these are resistant to proteolysis and slowly fill the lysosomes in neurons, cells which divide quickly being little affected—the lipofucin is diluted upon mitosis. It is only the neurons with a very slow mitotic rate which become crowded with crosslinked protein fragments. This lowers cellular metabolism and diverts energy away from reparative processes. Iron, of course, increases the rate of peroxidation considerably. The aluminum ion (Al³⁺)—although not capable of donating or accepting electrons—is though to catalyze this process indirectly by displacing the similarly‐sized iron (Fe³⁺) atom from binding sites, and also directly by crosslinking proteins at the phosphoryl groups (if present).

Terman, Alexei. "Lipofuscin." The international journal of biochemistry & cell biology (2004)
Cosgrove, John P. "The kinetics of the autoxidation of polyunsaturated fatty acids." Lipids (1987)
Koppenol, W. H. "Oxyradical reactions: from bond‐dissociation energies to reduction potentials." FEBS letters (1990)
Bielski, B. H. "A study of the reactivity of HO2/O2-with unsaturated fatty acids." Journal of Biological Chemistry (1983)
Huvaere, K. "Light-induced oxidation of unsaturated lipids as sensitized by flavins." The Journal of Physical Chemistry (2010)
Carini, Marina. "Mass spectrometry for detection of 4‐hydroxy‐trans‐2‐nonenal (HNE) adducts with peptides and proteins." Mass Spectrometry Reviews (2004)

 
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