Cunning, Baffling, Powerful

MorpheusThese are the words the AA big book uses, which other 12 step fellowships have adopted to describe their addictions.  But one thing I used to think is that alcohol kills brain cells, so how can overeating really be like that?  Well, here’s Morpheus, letting you know you can stop reading now, or see how deep the rabbit hole goes.

Opiates do not kill brain cells.  What they can do is light up the hedonic center in your brain, and some researchers say this should be the signature characteristic of addiction.  It probably explains Craving, or the motivation to use a substance despite adverse consequences.  But many things are pleasant.  What differentiates opiates from funny cat pictures?  Tolerance, or the need to take more of a substance to get an effect, and Withdrawal, the onset of deleterious symptoms when a substance is not taken.

The DSM5 spins these out in a list of 12 criteria, because they are focused on behavior and brain circuitry. But Tolerance and Withdrawal are questions of cell biology.  The brain is made of cells, but that is not why you shake, sweat, feel like bugs are crawling on your skin, and maybe even die from withdrawal.  They don’t explain why a usual amount of substance for a seasoned user might kill a first time user.  The reason is because the body produces enzymes that deal with the substance, one reason we talk of substance intoxication.

With regular use, these enzymes are expressed in increased amounts, and if the substance stops, the enzymes keep going for several days.  In the case of alcohol, they will find naturally occurring alcohols to attack instead.  In the case of opiates, they bind enzymes that make cAMP, so if they are removed, the enzymes are freed to make massive amounts of cAMP, which is similar to the effect that white and gold dress picture had on facebook.  No one could share, meme, or argue about anything else.  (Interestingly, caffeine and chocolate work cAMP from the other side, inhibiting its breakdown)

One reason cAMP is so significant in cells is that it indicates ATP is low. (cAMP is cyclic Adenosine Mono Phosphate and ATP is Adenosine Tri Phosphate).  ATP is the energy medium from the mitochondria to the cell.  The mitochondria charge the ATP with energy from turning carbohydrates into CO2 and H2O (hence carbo-hydrate).  At least, that is what they do when everything is decent and normal.

If there is more ATP than you need, the mitochondria will still make CO2, but rather than making water, they make oxygen radicals.  These are toxic, so your cell expresses an enzyme to deal with it.  The enzyme fixes the oxygen radical but also blockades the cell membrane so more carbohydrates don’t come in.  This is insulin resistance.  With the membrane blockaded, cells are loath to let anything else in or out, so blood vessel linings are hardened and brain cells can’t message each other very well, which is why mental sluggishness and depression are symptoms of insulin resistance.

This may seem like an extreme reaction, and it is.  Your cells have other feedback mechanisms to slow energy production when ATP levels rise.  But fructose is able to bypass these.  That is why high fructose corn syrup has been observed to cause insulin resistance in the liver particularly.  Those cells have the most mitochondria.  But table sugar is also half fructose.

Fats get around the blockade because they don’t need membrane transport.  The membrane is made of fatty acids, so fats can slide through on their own.  Once inside, they form the hub of the mitochondrial energy cycle.  (Acetyl CoA).  High fat diets have been found to increase insulin resistance particularly in the anxiety centers of the brain.

Even salt contributes to blockade running.  Membrane transport is the fastest way to get sugar into a cell, but there are other avenues, including a sodium enabled gate.  Normally, the cell might use 1/3 of its ATP pushing sodium out of the cell so it can pull sugar back through those gates.  But if you’re eating half your RDA of sodium in one sandwich, you get that sugar into the cell without using much ATP.

So sugar, fat and salt are substances that allow energy production to continue even after our cells have tried to shut it down.  The shut down is an enzymatic response to a toxin caused by energy production in the presence of high ATP.  Fortunately, you can use ATP by exercising.  Eating more than you need of any kind of food, or being sedentary can lead to high ATP and cell membrane blockade.

Everything has its time and place.  Alcohol, salt, sugar and fat are all preservatives of a kind, and they make it possible to eat food when we can’t grow it.  Our bodies make opiates when we are injured or run too far.  We need to store energy for winter, and the symptoms of insulin resistance like reduced mental activity and even infertility are part of that cycle.  That’s why our brains reinforce for these substances.  We just tend to put the cart before the horse.

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