Omega 3, dietary fish, and brain-lipid biochem insights - Andrew Kim Blog

Andrew Kim Blog: Brain food.

"Fish is brain food," is what I would hear in college from a roommate of mine who was seriously into his health.  He believed this so much that he would eat a piece of fatty fish before exams, and would urge me to do the same.  I was interested in health at the time, too, so I tried it.  Maybe I just didn't do it right or for long enough because I found that my friend's pre-exam ritual was a bad one, as was his reasoning for doing so, which was a physiological impossibility.
There is an ever-present belief that if a food contains a substance that is found in a particular body part, it follows inevitably that said food is beneficial for said body part.  I think this is what people really mean when they say that fish is brain food.  
The meat of fish and the brain both contain phosphorus, and before the hype about omega-3 fatty acids, phosphorus was thought to be the reason why fish was good for the brain.  Fish is actually a modest source of phosphorus, as there are many other foods that contain significantly more, and phosphorus is now known to be a minor element of brain tissue.

The physiology of the brain is complex, and it is, for all intents and purposes, the most sensitive to changes in energy availability--some areas of the brain more than others.  Some structural support is needed in the form of a phospholipid called lecithin and some of the B vitamins are needed to support oxidative phosphorylation, a deficiency of which will cause mental inefficiency, dullness, sleepiness, insanity, etc.  And adequate blood flow to the brain is also needed to supply nutrients—Including glucose and oxygen.
The extent of the brain’s sensitivity to fluctuations in energy availability, I think, is illustrated by studies in which people fasted for weeks to months.  Because the brain would waste away the slowest of all the organs, hardly any brain tissue would be lost at the end of such fasts.  Is it, then, any wonder that mental functioning at the end of these fasts was normal, nay better, in almost all cases?  To support fasts as long as these, the metabolism would have to decrease and the stress hormones would have to be secreted and maintained at high levels to convert the body's proteins to glucose and to mobilize fatty acids to convert to ketone bodies, which the brain would then use as an additional fuel source.  
I remember reading about Upton Sinclair, a social activist and card-carrying faster, who fasted, off and on, for a period of 6 weeks, in which he lost 25 pounds and wrote an entire play, one of his best and most creative works.  So deeply affected following on the heels of this experience, Sinclair was struck with the idea that the best poetry had yet to be written, and it would remain this way until poets cared enough to be prepared to feed their work with their own flesh.
The brain needs a continuous supply of food but it doesn't need huge amounts of it or all at once.  If this were so, our mental capacity would increase proportionately with the amount of food we ate. (A friend of mine, Heath Kurra, made the point that if this were true, the idea that meat eating led to bigger brains and greater intelligence would have a firmer basis in reality.)
Strictly speaking, realize that excess fat tissue, the product of eating more than what your metabolism can support is not necessarily benign and that health and strength usually return as soon as this excess is eliminated.  Because some people do, I'll mention that we should not express disapproval at the fact that fat is being lost, but rather look upon it as a sign of returning health.
Before I leave this train of thought, know that "excess" in this case is relative and there is no uniformly agreed upon objective standard as to what constitutes a healthy weight.  Be that as it may, if you have hypertension or diabetes, conditions that are inextricably associated with obesity, there's a high likelihood that the body fat you carry is excessive.
Given the adverse physiological changes that take place during a long fast, I've been racking my brain thinking about how these fasts were so effective as a cure for a long list of conditions.  A reduction of inflammation and body fat were undoubtedly at play, but, and this is the main objection to this practice I have, lean tissue would be reduced more than fat tissue, and some organs, like the thymus, wouldn’t fare as well as the brain.  Further, upon the completion of a fast, the metabolism would reset at a lower level from where it was before the fast, in part because of the loss of lean tissue, so that less food would be required for weight maintenance.  But I digress.
The main element of fish that is now purported to improve brain health are the long-chain omega-3 fatty acids.  Long-chain omega-3 fatty acids have a wide-range of drug-like actions in the body, but their main effects, including their famous triglyceride-lowering effect, appear to be carried out specifically by their breakdown products, that is, reactive carbonyl compounds, which can stick to proteins and to other biological molecules to form advanced lipoxidation end products (ALE), thereby impacting the functioning of the entire cell.
More generally, fatty acids make cells resistant to the hormone insulin and as a result, amino acids and glucose are wastefully converted to lactic acid, and the resulting local acidity allows more fatty acids to enter cells.1,2 These fatty acids can disrupt the cell, partly by decreasing the acidity of the carboxylic acid groups of proteins so as to favor the destabilization of intracellular proteins and the release of potassium and uptake of sodium and calcium, with a subsequent increase in density and decrease in viscosity. Unsaturated fatty acids are more thorough disrupters in this regard than saturated fatty acids are because unsaturated fatty acids also form fewer hydrophobic interactions with each other and are generally stronger acids.3 As cells accumulate increasingly more fat, these disruptive effects become increasingly more problematic. (For an easy-to-read explanation on the basics of cell physiology, read this.) Long-range, yet fundamental, biological effects such as these are hardly ever considered.
Fatty acids are able to slightly polarize the cell's water, as hydrogen bonds begin to form between water molecules and fatty acids, causing further hydrogen bonding among other water molecules.  The interaction between fatty acids and water, in turn, governs the way in which these now explicitly hydrated fatty acids interact with other proteins, or "receptors," and the way in which these proteins interact with other biological molecules.  Modeling of aqueous solutions should always consider the interactions with water, which is different from bulk water and anything but a continuum.  Investigations in the 1930s by Gortner et al., showed this to be the case, as they found that cellular water to which sucrose was added was less resistant to freezing compared to bulk water, indicating some inherent property of cellular water was resisting the dissolution of sucrose.4 This idea, however, was pretty much abandoned once the membrane-pump theory was widely accepted in the 1940s.
(Gilbert Ling later made the membrane pump theory untenable, showing that frog muscles without membrane pumps accumulate potassium and exclude sodium, just like cells with intact membranes do, and red blood cells with intact membranes and membrane pumps but without cytoplasmic proteins couldn’t move potassium and sodium against their concentration gradients.)
I think the mistaken idea that fish oil reduces insulin resistance in humans reinforces its unfavorable energetic effects.5–7 I’ve mentioned before that upon stimulation, PUFA are liberated into the cell and this is accompanied by the depletion of ATP through its conversion to cAMP, which, in turn, activates the aromatase enzyme that converts androgens to estrogens—interfering with the use of oxygen.  Certain prostaglandins promote the deposition of collagen by fibroblasts so as to increase the diffusional distance that oxygen has to traverse to reach cells, aggravating the cell’s deficiency of oxygen.  A deficiency of oxygen, in turn, promotes the accumulation of lipids inside cells by decreasing the breakdown of the protein portion of LDL particles, which is required to prevent the deposition and accumulation of lipids inside cells.
In addition to its effect on the cell’s viscosity, described above, the decrease in ATP accelerates lipid peroxidation processes, including the breakdown of free PUFA to lipid hydroperoxides, lipid hydroxides, unsaturated aldehydes, epoxyhydroxy acids, etc.  Many of these lipid peroxidation products are involved in age-related brain degenerative diseases, such as Alzheimer’s.8–10
I’ll eat fish occasionally as I think fish is a very good source of B vitamins, some minerals, and protein. (Trader Joe’s has a canned salmon product that is near completely devoid of fat, which I’ve been eating.)  But believing as I do, I don’t have any weird delusions that eating it will make me smarter or whatever.  And taking it as a supplement is no better.  It would be a perversion of facts to think otherwise.  The fact that some of the currently used drugs to treat conditions such as epilepsy and hypertension are incidentally showing to be protective against the neurodegenerative diseases speaks to a different paradigm of neurodegenerative diseases—a paradigm that has no place for the use of cholinergics and fish oil.