THE RANDLE CYCLE
By far one of the most important physiological processes to understand, particularly in the context of the Peatsphere, is the so-called Randle Cycle or Randle Effect.
If you listen to any interviews with our beloved bioenergetic Bulgarian
@haidut you will see it pops up regularly—and for good reason.
The Randle Cycle refers to the substrate competition between glucose and fatty acids for energy.
In plain English: when a cell is using carbs for energy, it struggles to use fat; and when it is using fat for energy, it struggles to use carbs.
This is important because the bioenergetic view holds that the inability to oxidize glucose for energy (and all it entails) is at the core of degenerative diseases such as heart complications, Alzheimer's, diabetes, cancer, etc.
I made this diagram hoping to elucidate this with a bit more detail:
(Forgive me, friends, I know all diagrams are inherently flawed, but I enjoy making them nonetheless. Just note that all of this is an oversimplification because cells don't operate like machines in which A → B → C all the time, and because players at a cellular level don't just interact through clear-cut mechanisms (e.g., "lock-and-key" interactions))
What the diagram says
When free fatty acids "activate" the Randle Cycle, they prevent proper glucose oxidation...
(1) Through allosteric inhibition of enzymes PFK1, Pyruvate Kinase, and PDH, crucial players in the breakdown of glucose/pyruvate so we can gather their electrons; and...
(2) Through metabolic regulation of the cell’s redox balance in favor of NADH* and FADH2**, into the so-called "reduced state" (i.e. a "slow and heavy" state, away from efficient oxidation).
* This inhibits PDH, the Krebs Cycle, and turns accumulated pyruvate into lactate. No bueno.
** This overloads Complex II in the Electron Transport Chain, thus increasing ROS (Reactive Oxygen Species, AKA "free radicals") generated in Complex I and increasing levels of NADH—thereby feeding a vicious cycle.
What the diagram means
When free fatty acids in the blood increase above a certain threshold (right side), they compete with glucose (left side) for uptake into the cell.
This is a rare case of quasi-binary switch in living organisms. Yes, cells can oxidize both carbs and fats, even some at roughly the same time, but overall it is easier for them to stick to one source of energy.
Think of it as a car that could somehow run on both gasoline and diesel at separate times, but would get overwhelmed if you poured a 50/50 mixed of both into its tank.
Except here, unlike with a car, your ability to use one fuel vs the other will be influenced by whichever fuel is being used most of the time. It's not that cells "forget" how to use carbs, but that the pathways to their proper use get burdened.
Peat mentioned this effect is seen almost immediately in hospitalized patients who are given an intravenous emulsion of soy oil, which leads to a rapid decline in their ability to metabolize glucose.
This explains why some people, like those doing long-term keto, have a seriously hard time reimplementing carbs into their day-to-day lives.
Doing so causes all sorts of problems, so they blame the carbs. But it was never "carbs themselves" that were problematic, it was their (in)ability to metabolize them.
Why this matters
The bioenergetic tradition believes efficient energy metabolism is central to health.
By ensuring health at a cellular level, you cultivate bottom-up health; by unburdening the particular (cellular health) you ameliorate the systemic (organismic health).
When I say “unburdening” our cells or metabolism in general, I ultimately mean allowing cellular respiration to occur as “efficiently” as possible: generating more ATP sustainably, and thus more of is protective byproducts like CO2, fewer of its risky byproducts like ROS, etc.
Doing this at an organismic scale—by discouraging processes, substances, etc. that inhibit it, and encouraging those that promote it—gives your physiology enough tools to really “do its thing”, unconstrained, relying less on adaptive stress mechanisms that, whilst practical in the short-term, lead to a plethora of long-term issues.
Thus, an "activated" Randle Cycle is problematic because you are potentially messing with a process central to life itself. By activating it you have two "opposed" energy substrates trying to shove themselves into a single cell, each cancelling the negentropic mission of the other.
This leads to all sorts of issues like wasting electrons in and out of the ETC (Electron Transport Chain), unnecessarily raising blood glucose levels, messing with the pancreas' ability to make insulin, promoting the production of AGEs (Advanced Glycation End-products) and just generally making a bit of a metabolic mess.
Basic practical info
- Obese people should be particularly careful vis-à-vis the Randle Cycle given that they have a superabundant supply of endogenous fat ready to clog things up.
- Speaking of being fat, a high-carb, high-fat diet will make you fat.
- On the other hand, a high-carb, low-fat diet could help you lose fat without wasting excessive tissue and whilst minimizing metabolic distress.
- Eating carbs ad libitum does not come without risks, however. One obvious challenge is they increase the metabolic rate, which means they increase the rate at which cofactors such as B-vitamins (particularly involved in carbohydrate oxidation) get "used up". Be careful and don't just shove sugar into your mouth.
- Short and medium chain fatty acids, like those found in coconut oil and goat/cow milk, don't seem to be subject to the Randle Cycle because they are metabolized more like sugars.
- Before Krusers et al. jump at my throat, it's definitely a good idea to get as much sunlight as you can without burning, and it will help you metabolize glucose.
- To the surprise (and, I'm sure, outrage) of many, the Randle Cycle seems to explain that it is the chronic oxidation of fat—not glucose—that leads to diabetes, and in fact an intelligent combination of carbohydrates and B vitamins has been proven to completely reverse diabetes.
- Finally, on the topic of B vitamins, if you suspect you have trouble metabolizing carbs, consider playing around with nutritional yeast (NY) or brewer's yeast (BY). Mix about 10 grams with boiling water, let the yellow deposits rest at the bottom, and drink the liquid. B vitamins are water-soluble, so you don't need the residue (in fact, it's best you don't drink it). When you take it, make sure to eat extra calcium (e.g., more milk, cheese, eggshells, calcium carbonate powder throughout the day) and maybe pop an aspirin to prevent the synthesis of estrogen, or rub a drop or two of Progest-E on your gums, if you have some. If you truly were deficient in some of them, you should feel its effects very quickly (1 h to 1 day). How those effects manifest will depend on many factors, but people report more mental clarity, sustained energy, and a feeling relaxed readiness.
That is all.
Thank you guys for reading.
If you made it all the way here say I wish you an endless supply of fresh grass-fed goat milk and nonallergenic, glyphosate-free honey.