Pregnenolone For Adrenal Fatigue?

Mark Volmer
8 min readApr 24, 2020

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Here’s a common remedy for adrenal fatigue — take some pregnenolone.

Ah, if only it were that simple…

Pregnenolone for adrenal fatigue is not the cure-all you think it is. Pregnenolone may actually make your adrenal fatigue worse!

The theory known as the pregnenolone steal is not one supported by evidence. Even though most practitioners claim this to be the cause of your symptoms. Pregnenolone supplementation might actually make your adrenal fatigue worse.

Today, you’ll learn everything to know about pregnenolone and adrenal fatigue. By the end of the article, you’ll know more than your practitioner!

Let’s get going!

Your HPA axis in action

Adrenal fatigue is dead. Rising from the ashes like a phoenix is adrenal fatigue v2.0. Known today as Hypothalamic-Pituitary-Adrenal Axis dysfunction (HPA-D).

When you’re stressed, who do you think interprets that signal?

Your brain. Not your adrenal glands. Your brain then sends signals to your body through two distinct pathways:

  1. Through your nerves
  1. Through your HPA axis
  2. Communication is done through a cascade of hormones.
  3. This system is used in response to periods of long-term stress.

The theory of your adrenal glands fatiguing due to stress isn’t supported by the evidence. Adrenal fatigue was a simplified theory used to explain a complex series of events your body undergoes when exposed to stress. It’s your brain that’s in charge of your body’s stress response. More specifically, the HPA axis.

That fatigue of yours, it’s not an adrenal problem. It’s a brain problem.

Let’s see how that affects the use of pregnenolone for adrenal fatigue!

Pregnena-what?

Pregnenolone. Many refer to it as the mother hormone. This label comes from pregnenolone’s ability to be synthesized into so many different hormones.

In order to make hormones, your body takes cholesterol and synthesizes it. The first hormone synthesized from cholesterol is often pregnenolone. To make other hormones like DHEA or testosterone, your body synthesizes the pregnenolone.

Here’s a quick look at some other hormones given birth to by pregnenolone:

  • Cortisol
  • Progesterone
  • DHEA
  • Aldosterone

Notice how all of the above hormones are known players in adrenal fatigue. And they all need pregnenolone in order to be synthesized. Thus, if you’re low in cortisol, it makes sense why you might think increasing pregnenolone will improve your adrenal fatigue!

Pregnenolone for adrenal fatigue

If you’ve got adrenal fatigue, you probably also have low levels of DHEA. If you run the DUTCH test, you might also notice that your sex hormones are low. Hormones like progesterone or testosterone.

A lot of practitioners conclude that low levels of hormones come about by way of a process known as the pregnenolone steal. Their thinking is this:

All steroid hormones need pregnenolone in order to get synthesized.

The high-stress situation common in adrenal fatigue will inevitably create a situation of lowered pregnenolone because it’s all being used to make cortisol.

Low pregnenolone means there is less available resources to create other hormones like DHEA, testosterone, or progesterone.

Said another way, in response to stress, your body needs to produce a lot of cortisol. Pregnenolone is the hormone needed to synthesize cortisol. In adrenal fatigue, your body is stealing pregnenolone in order to make more and more cortisol. This results in little pregnenolone left over for making other hormones like DHEA, progesterone, and testosterone.

This is what is known as the pregnenolone steal. It’s commonly discussed in practitioner circles as a consequence of adrenal fatigue. This is why many practitioners prescribe pregnenolone.

Adding more pregnenolone to your system should give more resources for other hormones, right?

Nope.

The pregnenolone steal isn’t a real phenomenon…

Debunking the pregnenolone steal in adrenal fatigue

Adrenal fatigue is a simplification of an incredibly complex process. The pregnenolone steal follows in the same vein. It’s a complex process oversimplified by the notion of simply stealing pregnenolone.

Here’s why the pregnenolone steal doesn’t stand up to scientific scrutiny:

Your adrenal gland consists of 3 different layers. Each of the three layers is composed of different cell types. The different cell types are responsible for secreting and synthesizing different hormones.

  1. Zona Glomerulosa
  • This is where the aldosterone hormone is synthesized.
  1. Zona Fasciculata
  • This is where the cortisol hormone is synthesized.
  1. Zona Reticularis
  • This is where the DHEA hormone is synthesized.

Cells of the Zona Glomerulosa are using cholesterol and pregnenolone to make aldosterone. Cells of the Zona Fasciculata are using cholesterol and pregnenolone to make cortisol. Cells of the Zona Reticularis are using cholesterol and pregnenolone to make DHEA.

There is no known pregnenolone storage system that cells can steal from. Pregnenolone is made within the mitochondria of each cell by using cholesterol. There is also no known mechanism that allows one cell to take pregnenolone from another cell.

The pregnenolone steal is an oversimplification of an incredibly complex process. It is not the way your cells operate. Consider the pregnenolone steal officially debunked.

Just in case I haven’t swayed your opinion yet, allow me one more opportunity…

Yet another reason why the pregnenolone steal is bogus

Cortisol follows something known as a diurnal rhythm. Meaning that cortisol levels fluctuate based on the natural light-dark cycle found on planet Earth.

In a properly functioning HPA axis, cortisol levels surge to their highest levels shortly after waking. Cortisol then slowly declines as the day progresses. Cortisol levels should reach their lowest point of the day shortly before bed. As you sleep, cortisol levels rise and the cycle begins again the next morning.

There’s a massive change in cortisol levels between when you wake up and when you go to bed. (1, 2) Levels of cortisol can decrease by almost 80%. All within a 24-hour period.

If the pregnenolone steal phenomenon existed, there would be plenty of time each day with low cortisol levels. Which would allow plenty of pregnenolone to be used in synthesizing other hormones like DHEA. But that’s not what you see happening!

This further illustrates that adrenal fatigue is not an adrenal problem. You cannot fix adrenal fatigue by supplementing adrenal hormones. Adrenal fatigue is a brain problem. To fix adrenal fatigue, you need to fix the brain.

Next, let’s see if pregnenolone supplementation improves adrenal fatigue…

Does pregnenolone supplementation improve adrenal fatigue?

Prescribing pregnenolone is predicated on the pregnenolone steal being an actual phenomenon. If you’re bought into the pregnenolone steal theory, then giving the body more pregnenolone makes sense. More pregnenolone means more available resources for your cells to synthesize other adrenal hormones like DHEA.

But since that’s been officially debunked, does pregnenolone supplementation help adrenal fatigue patients?

You need to stop thinking about adrenal fatigue as an adrenal problem. This way of thinking is furthering the issue. The interplay between your HPA axis and hormones is an incredibly complex network of events.

Your HPA axis communicates via feedback inhibitions, receptor signaling, genomic regulation, heat shock proteins, and many other hard to understand processes. Your adrenal fatigue condition is not caused by low pregnenolone levels. Low pregnenolone is a symptom, not a cause.

Consider the following:

The simple act of having high blood sugar (hyperglycemia) leads to a massive decrease in DHEA and pregnenolone leves. Massive!

In one study, praticipants DHEA levels decreased by an average of 57% only eighty minutes after a glucose injection. Pregnenolone levels also dropping by a whopping 51%. All within eighty minutes! (3)

1 in 3 North Americans have high blood sugar by way of diabetes. And another 1 in 3 North Americans have high blood sugar from pre-diabetes. That’s 2 out of 3 people in North America that likely have symptoms of adrenal fatigue.

No matter how much pregnenolone you give these people, they will not feel better. You need to address the root cause. And high blood sugar is clearly one such root cause!

The bottom line is this — supplementing pregnenolone may help with some of your adrenal fatigue symptoms. But low pregnenolone is not the root cause of your adrenal fatigue. Supplementing pregnenolone will not cure adrenal fatigue.

You still need to identify and treat the underlying issue affecting your adrenal health. Only then can you reach a cure.

Adrenal fatigue could actually be helping you…

I implore you to stop thinking about adrenal fatigue as a simple hormone deficiency. Taking this or that supplement to raise hormone levels is not the approach you should be taking.

Low pregnenolone, low cortisol, and low DHEA are all symptoms. They are not causes. You cannot fix the root cause of adrenal fatigue by treating simply giving hormones. To actually fix adrenal fatigue, you have to identify the underlying source or cause.

To further complicate matters, adrenal fatigue can be considered a healthy adaptation by your body. In these situations, the administration of hormone therapy could actually worsen your condition. Here’s why:

Cortisol is a catabolic hormone. Meaning that it breaks down tissue. No bueno.

In response to inflammation, let’s say a chronic infection due to mold, your body will release cortisol. In the short-term, this is a normal and healthy response to the stress of inflammation. Cortisol is anti-inflammatory after all.

But chronically high cortisol levels will cause atrophy to a specific region of your brain known as the hippocampus. (4) Yep, that’s the same part of your brain that atrophies in alzheimers disesae. The hippocampus is absolutely essential for all things memory related.

In an effort to protect itself, your brain lowers cortisol levels. Said another way, adrenal fatigue could actually be protective measure.

When you get all high and mighty thinking you’re going to fix this adrenal fatigue by taking hormones and supplements, you might actually be making the situation worse. Much worse. You might be contributing to the shrinking of your hippocampus!

If not pregnenolone, how do you fix adrenal fatigue?

By this point, if you’re not questioning everything you thought you knew about adrenal fatigue, go back and re-read the previous section. It’s so important.

Using pregnenolone and other hormones/supplements to treat your adrenal fatigue may actually worsen your underlying condition.

What to do?

You have to find the root cause. This is absolutely essential. Before you start pregnenolone or any other hormone therapy, find what caused the lowered levels to begin with.

Some of the most common root causes I see are:

  • Blood sugar abnormalities
  • This alone causes dramatic changes to DHEA levels.
  • Hidden sources of inflammation
  • Think stealth infections. Things like Lyme disease, mold illness, and Ebstein Barr Virus.
  • Using pregnenolone or any other hormone therapy before addressing the hidden infection will make you feel so much worse!

To be clear, I’m not suggesting pregnenolone never be used in the treatment of adrenal fatigue. Using hormones in treatment may still be necessary. Just be sure to use hormone therapy in the proper order. This means identifying the root cause of adrenal fatigue before throwing hormones at it!

Ok, now you know as much as I do about pregnenolone for adrenal fatigue!

It’s time for me to hear from you.

How was your experience using pregnenolone for adrenal fatigue?

Did pregnenolone make your fatigue symptoms better or worse?

Leave your answers in the comments section below!

Click here to learn the best practices to eliminate brain fog and achieve a clear, focused mind.

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Mark Volmer

I help those with fatigue naturally reclaim their energy and share their gifts with the world.