Wow, it’s been four and a half months since my last blog post so I’m guessing best case, my readership has fallen by half; worst case, I’ll be writing this post to myself. But it’s not my fault, and if it’s any consolation it hasn’t been enjoyable at all. I’ve been under the gun the entire time and basically subsisting on some of the best local brownies and cookies, which is fun in the beginning but eventually gets gross. The crankiness and recurring headaches I’ve been having are probably signs that I’m reverting back to my old ways and should probably step back to take a breath. But this blogging hiatus and mini burn out has opened the doors for me to again contemplate stress and fundamental ways to prevent and counteract it, starting all the way back from Hans Selye.
Not to get too off track but I'm continuously amazed by Selye's knack for bringing together disparate pieces of data to produce unified ideas, principles, and theories. Of course an important by-product of this gift was that it laid down the basics for what eventually became understood as the generalized stress response — the idea that the hypothalmic-pituitary-adrenal cortex pathway would become activated regardless of the quality or nature of a stressor.
Cortisol exposure is a major effect of activating this pathway. Because cortisol promotes fat metabolism while inhibiting glucose metabolism, more molecules of oxygen are consumed and fewer molecules of carbon dioxide are produced to permeate into the mitochondria, causing the mitochondrial respiratory system to operate less efficiently or improperly since oxygen is needed to maintain the cell in its living state and carbon dioxide (along with iron, NAD+, CoQ10, etc.) functions as a cardinal adsorbent would in mitochondria. Continued respiration is dependent on maintaining a “delicately poised” state of the respiratory proteins, which is largely dependent on these cardinal adsorbents, as the concentrations of potassium, calcium, sodium, and magnesium ions are relatively low and fixed. In essence the cardinal adsorbents allow potassium and magnesium — whose adsorption is required to generate ATP — to preferentially adsorb to important respiratory proteins at the expense of calcium and sodium.
On an even more basic level, an increase in acidity primes the enzyme that synthesizes ATP in mitochondria, and a change in electron density underlies the change in acidity (pKa) of ionizable functional groups. By adjusting the electron density of the respiratory proteins, cardinal adsorbents allow for the selection adsorption of one ion, potassium and magnesium, over others, and this process regulates the activity of the enzyme that generates ATP.
With fatty acid oxidation, reduction, excess calcium, ATP loss, magnesium loss, low oxygen, and cell swelling tend to predominate, whereas glucose oxidation, ATP(and/or magnesium), respiration, and oxygen tend to oppose these processes. Gerald Pollack says that in order to live we need structured water. But in order have it, we need ATP because to maintain the living state, cardinal sites need to be occupied by ATP. The mere presence of ATP changes the size and shape of mitochondria. ATP increases the efficiency by which ATP is generated and loss of respiratory control goes hand in hand with the loss of ATP.1
By increasing free fatty acids and promoting the oxidation of fat, cortisol promotes a reduced state in which ATP is released, NADH predominates over NAD+, calcium and sodium replace potassium and magnesium, and the use of glucose decreases. In effect and most fundamentally, excess cortisol, like other electron-donating cardinal adsorbents, perturbs the balance of the mitochondrial respiratory chain. And because an overly reduced cell state represents a “dead state,” and because an impairment of respiration is a non-specific process, and considering “cells form tissues, tissues form organs, and organs form whole organisms,” I can at least say this will lead to body wide problems — though I’m not able to say exactly what those problems will be. (Though I would expect organs most dependent on ATP — the heart and nervous system — would be most vulnerable.)
Characterized by a gradual loss of biochemical organization in cell cytoplasm, degenerative cellular processes are usually associated with disturbances in energy metabolism. Cell swelling is typical of these degenerative changes, with an increase in sodium inside cells; if severe enough, the mitochondria may swell, too. Inflammation compounds all these problems, which is why agents that block or limit histamine, prostaglandins, bradykinin, serotonin, neutrophils, monocytes, etc., are so important, especially as we age. The addition of ATP instantly reverses these degenerative effects. Adequate nutrition and a normal blood supply are essential as well. On the other hand, excessive fat oxidation reduces oxygen and predisposes to these degenerative changes, including the fatty infiltration of cells.
“Uncouplers” are usually seen as good and desirable for wight loss but they do so by disrupting the delicate balance in the respiratory proteins alluded to above. The classical uncoupler 2,4-dinitrophenol, an acidic aromatic compound, for instance, as an electron donating cardinal adsorbent disturbs the electronic balance of the respiratory proteins as to impair the delicate oscillatory nature of the respiratory proteins through which ATP is generated. In effect uncouplers favors the state in which the ATP generating enzyme becomes active, opposing the effect of ATP. And in the absence of potassium the continued exposure to uncouplers blocks respiration, leaving the cell in a dead, swollen state. Extra potassium is vital whenever uncouplers are involved. The swelling caused by uncouplers such as thyroid hormone, for instance, are almost immediately reversed by potassium (and ATP). Insulin, on the other hand, parallels the effects of ATP.
Low carbohydrate diet advocates often compare the effects of fasting to carbohydrate restriction; although superficial comparisons can be made, they are fundamentally different in their effects — especially with regard to the interest of the delicate balance of the mitochondrial respiratory proteins. Though both are fundamentally stressful, the effects of fasting are more measured and tends to reduce the body’s exposure to things that could further disrupt or interfere with continued respiration. The fasting literature is interesting, mainly because of the painstaking detail with which the cases of complete fasts were described (by authors such as Upton Sinclair) and because the conclusions that can be drawn from the cases are subject to less interpretation than those of carbohydrate-restricted diets. But most interestingly, considering the fact that the diseases largely characterized by underlying metabolic disturbances (e.g., cancer) were completely reversed by complete fasts, something carbohydrate-restricted diets cannot lay claim to yet, the net effect of fasting on respiration is probably slightly positive.
I intended to make this post about stress but I guess I failed because it quickly veered into the complicated hell that is cell physiology and low-carbohydrate diets, of which discussing has become a bane of my existence. But have I really veered off that much? I think a solid groundwork has been laid from which to discuss ways to stress proof ourselves from anything.2 I plan to continue to update as to how I’m doing and I’m thinking about including some of the things I’m doing to recover from my latest burnout and to prevent future burnouts. I think that would make for interesting discussion … if anyone is still reading this blog. Good night.
1 This can be quantified by way of calculating the respiratory control index
2 Straight up stole this term from Danny Roddy