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:
- Through your nerves
- This is known as the sympatho-adrenomedulary system.
- This system is used in response to periods of short-term stress.
- Through your HPA axis
- Communication is done through a cascade of hormones.
- 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.
- Zona Glomerulosa
- This is where the aldosterone hormone is synthesized.
- Zona Fasciculata
- This is where the cortisol hormone is synthesized.
- 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!
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Does fruit sugar, I am mostly talking about low sugar fruits, react that same way on blood sugar as table sugar? I have a killer sweet tooth. It is my drug of choice and I have been trying to mitigate it some by doing smoothies with protein and fruit to deal with it.
Hi, Lisa,
Great question. It totally depends on what makes the fruit sweet – glucose or fructose. Glucose will most certainly alter your blood sugar. Fructose won’t alter your blood sugar, but it will have other unwanted effects when consumed in excess. More info on that here – https://fatiguetoflourish.com/fatty-liver-foods-to-avoid/
M
“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. ”
This statement doesn’t make any sense to me. I hope you don’t mind a little criticism of your article. Supplemental Pregnenolone reliably and dramatically increases circulating levels of Progesterone, Allopregnanolone, and to a much lesser degree DHEA. All of which are products of the Adrenal gland. That alone proves that theadrenal cells (and probably gonads and brain) use circulating hormones as hormone precursors to carry out their functions. I would argue that there is no evidence that the entire adrenal cascade happens in situ in a single pass. My understanding is that pregnenolone is moved out of the cell’s mitochondria after being synthesized in order to not inhibit future pregnenolone synthesis from circulating LDLs.
Pregnenolone is the most abundant neurosteroid in the brain. While it can be made from directly from cholesterol locally, almost all of the steroids produced by the adrenal glands can independently cross the BBB and be used within the brain. They play a major role in all of the dynamic and so-called plastic functions of the brain. It is for that reason that people reasonably conclude that a lack of circulating hormones reflects a lack of available hormones in the brain and nervous system. While Pregnenolone alone may not cure CFS, anyone who is living with a deficiency of cholesterol and/or pregnenolone would be well advised to supplement and replace what they are lacking. When you understand the role that pregnenolone and it’s derivatives play in your brain’s ability to function, you’ll know that there is no virtue in living with an inadequate supply.
I have personally never had any success getting a doctor to take my low total cholesterol levels seriously. I’ve been told that a total cholesterol of 120 mg/dl makes me the model of perfect health. And, that my fatigue, anxiety, depression, and cognitive problems are unrelated to my cholesterol. With that kind of thinking, there is no way that any knight in shining armor is going to launch an investigation into a mystery virus or a deeper cause of my symptoms.
Years ago, I was sent to an endocrinologist to test my hormones and he said that my thyroid was fine and that while my sex hormones weren’t perfect, they didn’t explain my fatigue or my cognitive symptoms. My serum AM cortisol was mid to high but my 24-hour urine cortisol was in the bottom 20% of the range. He said I didn’t have Addison’s Disease so everything was fine with him. In regards to my cholesterol he just said eat more eggs. So I left thinking that my hormones were OK, even though my cholesterol was so low.
Moving forward, here in the US I can order my own labs through a variety of sources so I recently decided to order my own Pregnenolone test and it came back at 52 ng/dl (range 22-237). No doctor every bothered to check my Pregnenolone. That means I’ve likely been living for over 10 years with 25% of the Pregnenolone my brain and body need to function optimally! I just started to supplement with Preg. I used too high a dose at first and my levels went up over 500 ng/dl in the first week so I backed it way down and now they’re stabilizing at around 190 ng/dl.
I have no idea how much Pregnenolone will help or how much of my symptoms have been caused or exacerbated by it’s absence. Either way though, there is no way I’m not going to maintain optimal levels because it’s one of the few things that are within my power to do. Waiting for a viral diagnosis or a CFS “root cause” before I balance my hormones is just not an option. Even after the first week I’m feeling an improvement in stamina so I’ll take what I can get. Only time will tell.
Maybe I’ll check in in a few months and update. BTW, I’m not defending the Pregnenolone Steal theory, I’m just commenting on your article. Looking back at my labs it seems that I can make Cortisol on demand but that my total daily output is woefully inadequate. I think it’s reasonable to at least consider that the low cholesterol, low pregnenolone, and low cortisol output are related to each other.
Since I have found no dietary way under the sun to raise my cholesterol numbers, it makes sense to boost and support the Pregnenolone since it’s easy to do. After that I’ll be looking to optimize the other adrenal hormones as well. When you say that “Using pregnenolone and other hormones/supplements to treat your adrenal fatigue may actually worsen your underlying condition.”, you should also consider that allowing your brain to remain in a steroid deficient state may also worsen your underlying condition. Choosing to wait for a deeper diagnosis to treat a known hormone deficiency seems ill advised.
Sorry for such a long-winded post.
Hey, Dan!
Thanks for the comment. I agree, frank deficiencies of pregnenolone are best remedied with medication. I’m happy to hear that your condition has improved with said remedy.
You can, however, run into issue in the context of chronic fatigue syndrome. CFS results from cells entering hypometabolism – something much like the dauer state of nemotodes. This is an adaptive mechanism as ribotoxins are blocking the voltage-dependent anion channel into the mitochondrial matrix. As such, the cells are left relying solely on glycolysis for ATP production – a woefully inadequate means of energy production.
By taking hormone replacement like pregnenolone, you may be working against the adaptive mechanisms of your body. The resulting effect can be increased lactic acid production and an overall worsening of symptoms. Now, this is all assuming your CFS is coming by way of biotoxins. If not, I completely agree with everything you said.
Thanks for the comment!
M
Hi. I was diagnosed with Adrenal Fatigue when I was 21 years old and was weaning my first child. I had very low cortisol levels and high DHEA levels. At night my cortisol was below the lowest end of normal for night time. I experienced severe mood swings, anxiety, unexplained rapid weight loss, sickness with no symptoms but just severe fatigue and an “ill” feeling. I had been diagnosed in the past with PTSD since giving birth to my first child. I could not fall asleep well nor stay asleep. I had to eat before bed to stay asleep or get up to eat in order to go back to sleep.
My doctor prescribed me pregnenolone compounded 10 mg nightly. I made marked improvements. About a year and half later I was back to my old self.
Fast forward 8 years and a second child later, I had a car accident, a mild one. No injuries. A few small bruises. For the next three months I was very clumsy. Sliced my fingers a few times, tripped several times. I had such severe inflammation and fascia pain I had to get massage, acupuncture, and chiropractic care twice a week for two years after the accident.
Two years later I was diagnosed with hypothyroidism, positive for EBV, and fibromyalgia.
I’m taking pregnenolone sublingual drops as the pills don’t seem to do anything. I feel my nervous system has been damaged. I just don’t know where to turn to for proper advice. I grew up doing well in gymnastics and sports. I’m very in tune with my body. Yet somehow I have developed scoliosis and a weakness in my right side of my body. I get unexplainable random pain in my neck or shoulder leaving my arm and hand very very cold even blue. Yet my pulse ox is normal and X-rays showed no signs of dislocation, fracture, breaks, or tears.
I do have trouble detoxing. My mitochondria, I think, don’t function properly. Then again, where does this leave me? Who will listen to me or know the first step to helping me?
Rheumatology didn’t see these symptoms the very day I was in her office so she dismissed me like I made it all up. Endocrinology say I was misdiagnosed with my adrenals and my thyroid. Yet if I stop medication my hair falls out, my fatigue and depression are worse, etc. It’s so frustrating! I feel like I have no one who will listen.
Nice article and the convo you and Dan had was a mic drop. Good job guys way to handle it.