Click here to go to part 5, Neuroscience Takes A Spin On The Wheel.


What has been will be again, what has been done will be done again.

– Ecclesiastes 1:9

I know that I am mortal by nature and ephemeral, but when I trace at my pleasure the windings to and fro of the heavenly bodies, I no longer touch earth with my feet. I stand in the presence of Zeus himself and take my fill of ambrosia.

– Claudius Ptolemaeus (a.k.a. Ptolemy)

To know that we know what we know, and to know that we do not know what we do not know, that is true knowledge.

– Nicolaus Copernicus

Around nineteen hundred years ago, the Greco-Egyptian astronomer Ptolemy devised an ingenious way of thinking of the heavenly bodies.  Contrary to popular thought, the western world by this time did not believe in a flat Earth, but widely considered the Earth to be a sphere floating is space.  In fact, Pythagoras in the 6th century before Christ taught that the Earth was a sphere.  Plato and Aristotle thought so, as did most people who were relatively educated.

Not only did the ancient world believe that the Earth was a sphere, they had a pretty good idea of just how big this sphere was. A whole 250 years before Augustus Caesar ruled Rome, the Greek Erastosthenes made a remarkably accurate calculation of the Earth’s circumference by measuring the angle of shadow of the sun at high noon in two different locations.

How Erastothenes calculated the circumference of the earth in 250 BC without leaving Egypt.  The guy also accurately calculated the earth's tilt.  Obviously, he, Ptolemy, and Copernicus were amazingly brilliant.  Courtesy Wikipedia.

How Erastothenes calculated the circumference of the earth in 250 BC without leaving Egypt. The guy also accurately calculated the earth’s tilt. Obviously, he, Ptolemy, and Copernicus were amazingly brilliant. Courtesy Wikipedia.

Ptolemy took this knowledge of a spherical Earth existing in space and hypothesized that the sun, planets, and stars cycled around the Earth, which was the center of his universe.

However, it became obvious that these circular orbits did not match observations of how the celestial bodies actually moved.  Since Ptolemy favored the elegance of a circle, he devised a way around this dilemma.  The celestial bodies did not just orbit in a circle.  They orbited in circles within circles.  Or, to use his terminology, epicycles within cycles.

A medieval schematic of celestial cycles and epicycles in a Ptolemaic universe.

A medieval schematic of celestial cycles and epicycles in a Ptolemaic universe.

It was not until around 1400 years later that Copernicus ushered in his “revolution” that showed that the Earth was not the center of the universe, but rather one of the planets that revolved around the sun.  Even so, Ptolemy’s model, with its cycles and epicycles, had become so useful and sophisticated that it was still used for some time even after Copernicus’ revolution, as it oftentimes made better predictions of what the heavenly bodies were going to do.

As time passed and Copernicus’ model evolved, it eventually surpassed Ptolemy’s in accuracy.  New technology allowed for better observations which allowed for further refinement.  Tycho Brahe, then Johannes Kepler, then Isaac Newton, then Einstein, among numerous others, came along and built upon each other, creating models which ever more accurately represented how things really are.

Yet, even though Ptolemy’s geocentric universe is incorrect (and technically, Copernicus’ heliocentric universe is also incorrect – there is no center of the universe), Ptolemy was right that within our universe are an abundance of cycles and epicycles.

In other words, Ptolemy was wrong only in the particular applications of his model.  But the idea of recurring cycles within cycles (or wheels within wheels as I like to say) has come back with a vengeance.  It is now clear that the idea of cycles and epicycles is more fundamental to the universe than even Ptolemy imagined.  And not just in cosmology, but biology.

In other words, Ptolemy’s universe is back, just in a different form.  As King Solomon would say, “What has been will be again, what has been done will be done again.”  Or as Nietzsche, or people still selling bell bottoms would say, there is an eternal recurrence.

Let’s look at a few examples.

An electron on the surface of the Moon cycles around a bundle of protons and neutrons (a.k.a. an atomic nucleus).  But this is an epicycle as the surface of the Moon cycles around its center.  The Moon cycles around the Earth.  But this is an epicycle as the Earth cycles around the Sun.  Even the Earth cycling around the Sun is an epicycle as the Sun sits on one of the spiral arms of the Milky Way and cycles around the galactic core.

Likewise, the wheel of fire has cycles and epicycles.  It has wheels within wheels.

In order to explore some of these wheels within wheels, let us consider our now more expanded, broader outline of the wheel of fire.  In BSSHM we considered the many ways in which the sex hormones are related to the metabolic syndrome.  In this series, this model is expanded to include numerous other interactions, primarily involving the HPA axis, neurosteroids and neuroinflammation, and other hormonal systems such as the hypothalamic-pituitary-thyroid axis.

Thus, while the more rudimentary wheel of fire looked like this:


A somewhat more comprehensive wheel of fire would look like this:


It should go without saying even this expanded wheel of fire is a vastly simplified version of reality.  Nonetheless, this more fleshed out wheel at least recognizes some of the roles of the major physiological players.  It also emphasizes how it is possible to start with any one player.  From this origin, any particular player may cause an amplification of any other player, which can then cause overlapping feedback loops, all causing an amplification of the original.

So, a more fleshed out wheel of fire would include a few of the diseases that have been mentioned already, such as major depressive disorder, chronic pain syndromes, and chronic psychological and physical stress.  It would also touch on many other common diseases, such as osteoarthritis, gastrointestinal disturbances (such as non-alcoholic fatty liver disease and gut dysbiosis), and various autoimmune diseases.  One representation of these relationships could look like this:


Thus, not only is the inner cycle of the wheel of fire self-reinforcing, but because of its relationships with various diseases, all of these diseases may be self-reinforcing.  What is more, each of these diseases is not a point, but something of a positive feedback loop in and of itself.  Put another way, if you zoom in on each pathology, whether that be depression or chronic pain, it becomes apparent that these are epicycles.

Let’s consider a few examples.

Major depressive disorder frequently leads to lethargy and sleep disturbances.  Lethargy and sleep disturbances lead to loss of muscle mass and increased visceral adipose tissue.  Increased VAT leads to neuroinflammation, decreased testosterone, and worse depression.

This is a cycle.  But it is a epicycle within the larger cycle of the Wheel of Fire.


Chronic pain syndromes causee chronic sympathetic activation.  This eventually causes neurosteroid exhaustion similar to depression and anxiety.  The sex hormones are secreted insufficiently, or fail to work properly. This chronic pain also causes the person suffering to move in ways that lead to muscle atrophy, loss of mobility, and microscopic damage to the musculoskeletal and cardiovascular tissues.  This causes worse pain.  While this is a vicious cycle, it is only an epicycle in the larger scheme of things.


Chronic psychological stress leads to persistently elevated sympathetic tone.  Chronic inlfammation ensues.  Peripheral T4 to T3 conversion decreases and the rate of reverse T3 breakdown slows, increasing its levels.  Changes in behavior, cortisol, and sex hormone levels predispose to putting on fat.  Mood becomes progressively worse.  There is an increased propensity to stay inside, not exercise, and never seen sunlight.  This leads to worsening psychological stress and anxiety.


These epicycles are distinct in that they form their positive feedback loops.  One promotes another which promotes the one.  But they are also tied into the larger system of the wheel of fire.

By this mechanism, it becomes apparent that every onramp to the wheel of fire, whether it be a traumatic brain injury, chronic psychological stress, a failure to eat healthy food, changes in gut microbiota, or any number of other things, can act as a self-propagating epicycle.  And they can be tied in to numerous other epicycles.

While this model is by no means a complete representation of how billions of behavioral patterns, environmental factors, genes, epigenomes, proteomes, and everything else interact to form the wheel of fire, it provides us with a more accurate conceptual framework.    And while it is nice to have a more accurate framework showing how the wheel of fire is made of cycles and epicycles, its true value is not just in expanding our conceptions.  Its true value is in how it creates stronger heuristics allowing for the creation of better diagnostic and treatment tools.

In the next and final part of this blog series, I will briefly consider how this may be done.

This concludes part 6 of the Wheel of Fire: Cycles and Epicycles.

Click here to go to part 7 of the Wheel of Fire: An Intention to Treat