Before we start, kudos to Dr. Stephan Guyenet who came out with an amazing article absolving sugar of many of its supposed harms. Many thanks to him for publishing a progressive and ballsy piece of work.
This (long) article will be review for many, but will focus on why carbohydrate (predominantly fruit, but honey and simple syrup as well) is an optimal main source of fuel.
Familiarizing yourself with serotonin, oxidative energy, and the importance of calcium will increase the readability of this article.
The Anti-Stress Fuel
If you'll remember from my primer on Dr. Peat, energy and structure are interdependent. This suggests that energizing the cell will have a beneficial "ripple effect" throughout the entire organism. Put simply, "regeneration" cannot happen without efficient oxidative energy:
"I see the interaction between the flow of energy (e.g. between a sugar and oxygen) and the structure as one in which the flow is retarded by the structure, and used by the structure, in maintaining and complexity itself. (Another way of looking at this is that if energy can do something, it does something; and what it it does is build structure. The life structure is a kind of energy charge, but the important thing is the spontaneous nature of the interactions, in the presence of an energy supply.) The chemical nature of the energy source (and the energy "sink," which is usually oxygen) influences the nature of the structure-building." -Ray Peat
The cells cannot be energized without the active thyroid hormone, triiodothyronine (T3). The largest chunk of T3 is produced in the liver by an enzymatic conversion of thyroxine (T4) into T3 by the deiodinase enzymes.
Keeping the liver "energized" is an important factor in thyroid health. The inability to store glycogen, the storage form of sugar, can decreases the conversion of T4 to T3.
Stressful situations require more glucose. Once something has interfered with our ability to produce energy (a great stress), adrenaline is released to mobilize glucose from the liver to provide the missing glucose to help overcome the stress:
"...This increased consumption of glucose tends to lower the concentration of glucose in the blood, and this (or various other signals, such as pain or fear, that are associated with the need for more glucose) causes the secretion of adrenalin, which can mobilize glucose from the liver's glycogen stores. If the glucose stores are depleted, the body resorts to the secretion of cortisol, to provide glucose (and other material) by cannibalizing protein from tissues which are momentarily less essential." -Ray Peat
This suggests that low blood sugar is analogous to stress. Chronic low blood sugar makes one susceptible to the release of adrenaline and cortisol and is even more likely if liver glycogen is low (fructose avoidance, low thyroid).
Carbon Dioxide (CO2)
Before we dive into the follies of using fat as a main fuel source, let's discuss sugar's relation to carbon dioxide.
A highly efficient way of producing energy is called an oxidative metabolism. Oxidation refers to the mitochondrial use of oxygen to produce carbon dioxide (CO2) and energy (ATP):
"In old age, a person's life expectancy strongly depends on the amount of oxygen that can be used. When the mitochondria can't use oxygen vigorously, cells must depend on inefficient glycolysis for their energy." -Ray Peat
Low levels of oxygen interrupt this process, shifting the cells energy production to glycolysis; a drastically less efficient way to obtain energy.
Optimizing the production of carbon dioxide relies on using carbohydrate as a main source of fuel:
"When carbon dioxide production can be measured at the same time as oxygen consumption, it's possible to estimate the proportion of energy that is being derived from glucose, rather than fat or protein, since oxidation of glucose produces more carbon dioxide than oxidation of fat does. Glucose oxidation is efficient, and suggests a state of low stress." -Ray Peat
Moreover, low CO2 levels promote the inflammatory stress cycle causing platelets to "spill" serotonin instead of being detoxified in the lungs:
"The blood platelets that become incontinent and leak serotonin in the absence of carbon dioxide are undergoing the same structural stresses experience by endothelial cells, smooth muscle cells, mast cells and all other cells when carbon dioxide is depleted." -Ray Peat
Running On Fat Promotes Stress
Using fat as a source of energy is a feature of aging; it is truly a secondary fuel... I know, shift of paradigm... Again.
In the face of low glycogen, adrenaline will mobilize free fatty acids for fuel. The release of free fatty acids can inhibit the proper use of sugar via the Randle cycle:
"The last of these mechanisms, discovered by Denis McGarry and Daniel Foster in 1977, provides an almost exact complement to the mechanism described in the glucose-fatty acid cycle whereby high concentrations of fatty acids inhibit glucose utilization. These additional discoveries have not detracted from the important of the glucose-fatty acid cycle: rather, they have reinforced the importance of mechanisms whereby glucose and fat can interact."
- From: Rob Turner (PUFA Causative in Diabetes – Randle Cycle) more studies in the link.
While adrenaline is busy mobilizing fat (if glycogen isn't sufficient) cortisol is released to break down structure (thymus, muscles), into amino acids, and then into glucose.
Some of these amino acids, specifically tryptophan, further potentiate the stress inflammatory cycle:
"Both adrenaline and serotonin will stimulate the release of cortisol, which mobilizes amino acids from tissues such as the large skeletal muscles. Those muscles contain a large amount of cysteine and tryptophan, which, among other effects, suppress the thyroid.
The increased tryptophan, especially in the presence of free fatty acids, is likely to be converted into additional serotonin, since fatty acids release tryptophan from albumin, increasing its entry into the brain. Free fatty acids and increased serotonin reduce metabolic efficiency (leading to insulin resistance, for example) and promote an inflammatory state." -Ray Peat
Chris Masterjohn has also suggested that free fatty acids are involved in inhibiting thyroid signaling:
"There's good preliminary evidence that any unsaturated free fatty acids are quite good at inhibiting thyroid function. Not just PUFA but oleic acid is pretty good at it too. You can't do anything to suppress oleic acid because your body can produce it itself. PUFAs play a role, but you have a lot more oleic acid in the body.
Basically, any release of free fatty acids will inhibit thyroid signaling. The best evidence for this is at the level of thyroid binding to the nuclear receptor and then binding to DNA. It seems that the concentrations of free fatty acids can get high enough in the nucleus of the cell to inhibit signaling there and that will not be reflected in free T3 levels in the blood or anything like that. It would be very difficult to detect it clinically." - Chris Masterjohn