The Cause of all Disease: Simplified

The Cause of all Disease: Simplified
Scott Resnick MD 2023

Too often in natural health, we jump on the latest supplement trend diet, fad, or guru, and give it a whirl. But too often we fail to understand our physiology works from an ancestral perspective.

To begin with, humans are remarkably well built for survival, and historically our greatest stressor has not been crappy bosses, cheating, boyfriends, or traffic jams, but starvation.

Let’s take a moment to evaluate this from a physiological perspective. When I open my biochemistry book and read about cortisol, the opening sentence states that cortisol’s job is to regulate our blood sugar, not run away from the tiger.

Cortisol, the “King” of the Stress Response

In fact, cortisol’s response to starvation occurs on a diurnal basis, meeting daily. This is why we see a 3-4:00 AM spike on a four-point cortisol study. We ate our last meal before the sun went down and we crawled into our cave with the sunset. But at 3:00 AM, we haven’t eaten for eight hours, so cortisol‘s first job every night is to maintain our blood sugar throughout the night as we are in a relative state of starvation. We are fasting, sleeping and not up foraging for food.

Under perpetual stress, our cortisol, and DHEA initially rise. But when the stress is chronic and ongoing, our brain suppresses the adrenal response. This flattening of the cortisol response is what many of us refer to as adrenal fatigue. But the adrenals don’t really fatigue. They are instructed to under function by the brain.

In biochemistry, there are three “counter-regulatory” hormones whose job is to oppose the effects of insulin. One is cortisol. The other two hormones are epinephrine and norepinephrine.

If you are one of the people who bolt up from bed at four in the morning, it could well be from low overnight cortisol and the need to regulate your overnight fast with– you guessed it– adrenaline.

And for someone with a flattened cortisol curve throughout the day, this process repeats. We are either trying to control our low blood sugar with bursts of adrenaline, or we are making frantic runs to the cookie jar.

So now take a moment to examine how all of this fits together. Our default mode is to keep the heart and brain alive and to do this we preferentially use glucose, but we can also make do with catabolized proteins and fats.

Our Stress Response is About Starvation, NOT Deadlines

Now, imagine yourself in your cave with your caveman husband. It has been a long winter, the crops didn’t come in, and your tribe didn’t kill the buffalo in the fall migration. You’re hungry, and there’s no food around. What happens?

First, we begin to release the stress hormone cortisol, which I believe is the “King of Hormones”, as it directs all downstream functions with the intent of keeping us, a hungry animal, alive.

We first burn our fat. This is a great choice if you have to carry your survival energy on your skeleton because it yields 9 calories per gram in contrast to the 4 calories per gram found in carbohydrates and proteins.

With cortisol, we begin to break down our muscles and our organs. But this process began long before the day that we were born. A fetus under perpetual stress has a smaller abdominal circumference, which can prompt a high-risk obstetrician (with her patient) to make some choices. This is because the fetus’s liver has shrunk, metabolizing all of its stored glycogen and proteins. This metabolic compensation is revealed on ultrasound with a smaller belly. The placenta isn’t working well; sufficient glucose isn’t being delivered to the fetus; catabolism of the glycogen in the liver ensues; and the size of the liver shrinks.

When we are under stress and not eating (read: IF), there’s no reason to deliver blood through the mesenteric vessels to the gut. And here’s where things start to fall apart.

This is because the gut is highly metabolically active. The mucosal, single-cell lining regenerates itself every 3 to 4 days. But you can’t do that if you are nutritionally deficient and under stress. By definition, your cortisol is diverting blood from the gut to the higher-value organs like the heart and brain.

High Cortisol=Low Thyroid

Let’s take this a step further. If we are just trying to survive without food, why not dial back our metabolism? Is it any wonder then that we would get into a relatively hypothyroid state and produce increased reverse T3, the doppelgänger of T3? Under stress, we move to a state of hibernation, and thyroid hormone (through the pituitary and TSH) drives the bus.

What’s more important when you were trying to survive? Silky hair, nice eyebrows, radiant skin, and a thunderous libido? All that goes to the back burner as we struggle to survive.

But this gets even more interesting when you realize that we have both stressors with an ongoing high carbohydrate calorie intake. Cortisol by definition inhibits insulin receptor function. Our glucose is not able to enter the Glut-4 receptor in our insulin-sensitive cells but is gratuitously picked up in our fat cells, which lack this insulin-dependent receptor.

This is where the chronic cycling begins, because as we all know these fat cells make plenty of estrogen and pro-inflammatory cytokines.

Cortisol‘s secondary job is to suppress immune function. And here’s where the down-trending cycle perpetuates.

Gut Health Starts with Low Cortisol

General surgeons have known about the leaky gut in trauma for 40 years, observing that shock patients without any trauma to the abdomen were releasing LPS into their bloodstream. LPS is a molecule that sends the immune system into a tailspin, precipitating multi-system organ failure. Its source? Gram-negative bacteria in the gut.

With high cortisol and low thyroid function, we now begin to lose the integrity of our two principal barriers to the opportunistic, microbial world: our skin and our gut.

In a working model, when we are nutritionally sound and our insulin, thyroid, and cortisol are balanced, our skin and gut barriers remain intact. We can protect ourselves. It is my belief that this constellation of processes, in addition to all of the additives and crap that so many people eat, is strongly contributing to the fact that 12% of Americans have an autoimmune process. It is said that 75% of our immune cells lie just below the lining of our gut. So as our gut barrier breaks down, the underlying immune cells are maintained in a state of activation, and it’s “off to the autoimmune races”.

How to Detox Sensibly

And this brings me to the detoxification process, which is energetically demanding. How, then, are we able to detox if we lack cysteine for glutathione, lack B vitamins for the methylation process, and have a porous gut and cracking skin? We can’t. So, if your doc is promoting “detox” without considering these other factors, don’t be surprised if you are still feeling toxic.

And here, finally, is where progesterone comes in. If you are God or Nature (or whoever designed the human animal, I believe it was a little of both), and your precious creation is stressed, starving, inflamed, and barely making it, does it make sense that she would lose 80 ccs of life-sustaining blood every month? Of course not. As stressors increase, women move to a state of anovulation. It all makes sense. Our physiology sets us up to survive, well-practiced from long before 24-hour grocery stores and McDonald’s.


I was hoping to leave this group with an expanded perspective of what drives an estrogen dominance state. It is not simply low progesterone, but a consortium of other factors that are working in concert. The bottom line is that we need to approach our health systematically with a respectful eye to the processes, priorities, and physiology that have kept us going on this planet for so many years.






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