# Pregnenolone

Category: Hormones

To produce pregnenolone, thyroid, vitamin A, and cholesterol have to be delivered to the mitochondria in the right proportion and sufficient quantity. Normally, stress is balanced by increased synthesis of pregnenolone, which improves the ability to cope with stress. Lipid…

11 passages · 1 author · 1994–2022 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/pregnenolone

## Synthesis

**Pregnenolone** is the *master steroid hormone*, the first substance synthesized from cholesterol within the mitochondria, from which all other steroid hormones are derived. [Source 9] Peat argued that its production is fundamentally dependent on the delivery of **thyroid hormone**, **vitamin A**, and cholesterol to the mitochondria in the right proportion. [Source 4] When this system is compromised by factors like lipid peroxidation from unsaturated fats, energy deficiency, or hypothyroidism, pregnenolone synthesis fails, leading to a compensatory over-production of cortisol. [Source 4] Peat explicitly rejected the "pregnenolone steal" theory as a mechanical oversimplification, insisting that a well-nourished body naturally produces enough pregnenolone and progesterone to inhibit the stress systems, and that deficiencies arise from a lack of supportive factors like thyroid hormone, not a simple substrate diversion. [Source 1]

The physiological role of pregnenolone is to provide a buffer against stress and degeneration. Peat observed that in healthy, unstressed individuals, even massive doses produce no detectable hormonal changes, but in stressed or sick organisms, it normalizes elevated cortisol. [Source 7, 8] He described this as a *saturation effect*: once cortisol is brought down to normal, additional pregnenolone has no further hormonal action. [Source 7] Its protective effects are wide-ranging, including improving memory and performance, protecting brain cells from excitotoxic damage, and restoring youthful properties to aged skin by improving circulation and contracting muscle-like cells. [Source 2, 8] Peat noted that pregnenolone stabilizes the **cytochrome P-450 enzyme system** against degradation, which he believed was a general mechanism explaining its anti-toxic and anti-hemolytic effects. [Source 8] It also tends to normalize the function of the thyroid and other glands, which accounts for its broad benefits. [Source 2]

Clinically, Peat used pregnenolone as a primary intervention for conditions rooted in stress and hormonal deficiency. He reported dramatic, near-instantaneous effects, such as the recession of bulging eyes in **Graves' disease** within an hour, and the rapid improvement of joint mobility in arthritis and tissue elasticity in emphysema. [Source 10] He considered the agitated depression involving elevated cortisol to be primarily a pregnenolone deficiency. [Source 6] For supplementation, Peat found that a single oral dose of roughly 300 mg could remain active for about a week due to intestinal recycling and its ability to improve the body's own production. [Source 2] He personally experimented with doses ranging from a pinch to several grams daily, noting the main side effect was a tightening of loose skin and a more youthful appearance. [Source 5] He advised that sometimes an initial dose of a few hundred milligrams is needed to lower cortisol, and that it converts to either **DHEA** or **progesterone** based on the body's needs, offering an advantage over supplementing those hormones directly. [Source 1, 3, 6]

Peat and Dinkov discussed why pregnenolone was never adopted by the pharmaceutical industry. Peat explained that like progesterone, pregnenolone is a non-patentable substance that supports the body's endogenous production rather than suppressing it, making it a "terrible drug" from a commercial standpoint because it tends to cure diseases rather than create dependency. [Source 11] He noted that a 1950 symposium had already revealed its curative effects, but the drug industry had no interest in its very generality, which made it seem unlike a drug. [Source 2, 11] Dinkov questioned why it was never developed as a universal hormone replacement therapy, given its role as the precursor to all steroids. [Source 11] Peat affirmed that if made available massively and cheaply, pregnenolone, along with progesterone and DHEA, could essentially cure most of the current degenerative and stress-related diseases. [Source 11]

## People also ask

### How does thyroid function affect pregnenolone synthesis?

Peat argued that pregnenolone production depends on thyroid hormone, vitamin A, and cholesterol reaching the mitochondria in proper proportion, and that hypothyroidism causes synthesis to fail, leading to excess cortisol.

### Why did Peat reject the "pregnenolone steal" theory?

He considered it a mechanical oversimplification, insisting that deficiencies arise from a lack of supportive factors like thyroid hormone rather than a simple diversion of substrate toward cortisol.

### What did Peat observe about high-dose pregnenolone in stressed versus healthy people?

He noted that in healthy individuals even massive doses produced no hormonal changes, while in stressed or sick organisms it normalized elevated cortisol, describing this as a saturation effect.

## Related concepts

- [Graves' Disease](https://bioenergeticoracle.com/md/concepts/graves-disease/index.md)
- [Albumin](https://bioenergeticoracle.com/md/concepts/albumin/index.md)
- [Alzheimer's and Dementia](https://bioenergeticoracle.com/md/concepts/alzheimer-s-and-dementia/index.md)
- [Anemia](https://bioenergeticoracle.com/md/concepts/anemia/index.md)
- [Cytochrome P450scc.](https://bioenergeticoracle.com/md/concepts/cytochrome-p450scc/index.md)
- [Dehydroepiandrosterone (DHEA)](https://bioenergeticoracle.com/md/concepts/dehydroepiandrosterone-dhea/index.md)

## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — Pregnenolone

Ray Peat · Email · 2015

> # Pregnenolone
>
> Ordinarily, you can make enough from converting sugar to cholesterol, with thyroid and vitamin A converting cholesterol to the other hormones. But when you have been poisoned with not enough of the needed foods, or too much of the unsaturated oils, heavy metals, causing free radical reactions and so on, then it helps to use all of the supports possible, thyroid supplements, pregnenolone supplements, possibly dhea and progesterone, saturated fats, sugar, everything that works in the same direction.
>
> Pregnenolone is a lipid, only pharmaceutical salesmen talk about the need for a lipid matrix. Most people don't have allergic reactions to the rice and magnesium stearate.
>
> [BAD RESPONSE TO PREG] I think that would be from impurities in the pregnenolone. In animal studies, a dose equivalent to about a pound in a person, caused no change, unless the animal was stressed, and in that case it stopped the stress.
>
> [PREGNENOLONE 'STEAL' THEORY] Regarding the pregnenolone steal theory, It would be interesting to know who started that, it's a mechanical way of thinking about physiology that ignores the things that really matter. thyroid hormone, vitamin A, and cholesterol support the formation of pregnenolone, and the well nourished body is able to make large adjustments in these, to minimize the need for cortisol. In health, enough pregnenolone and progesterone are produced to inhibit the stress systems, for example by inhibiting the release of ACTH. When something prevents the formation of pregnenolone and progesterone, rising ACTH will increase its production as conditions permit, but if something, such as thyroid hormone, is lacking, the ACTH will increase cortisol, often with DHEA and the androgens increasing too, if resources permit; sometimes the stressed system is able to sustain only cortisol and aldosterone production, and that leads to degenerative problems.
>
> Someone recently tested pregnenolone for Beyond a Century, and said it looks pure. Sometimes at first a few hundred milligrams are needed to lower cortisol.
>
> [Is there anything different about taking pregnenolone for someone with a personality disorder, such as psychopathy or borderline personality disorder?] No.

### Source 2 — From PMS to Menopause: Female Hormones in Context

Ray Peat · Book · 1997

> **Ray Peat:** This coincides with the body's decreased ability to produce an abundance of pregnenolone. When aging rats are given a supplement of pregnenolone, it immediately improves their memory and general performance. Human studies, as early as the 1940s, have also demonstrated improved performance of ordinary tasks. It is now known that pregnenolone is one of the major hormones in the brain. It is produced by certain brain cells, as well as being absorbed into the brain from the blood. It protects brain cells from injury caused by fatigue, and an adequate amount has a calming effect on the emotions, which is part of the reason that it protects us from the stress response that leads to an excessive production of cortisone. People feel a mood of resilience and an ability to confront challenges. Many people have noticed that pregnenolone has a "face-lifting" action. This effect seems to be produced by improved circulation to the skin, and by an actual contraction of some muscle-like cells in the skin. A similar effect can improve joint mobility in arthritis, tissue elasticity in the lungs, and even eyesight. Many studies have shown it to be protective of "fibrous tissues" in general, and in this connection it was proven to prevent the tumors that can be caused by estrogen. Pregnenolone is largely converted into two other "youthassociated" protective hormones, progesterone and DHEA. At the age of 30, both men and women produce roughly 30 to 50 mg. of pregnenolone daily. When taken orally, even in the powdered form, it is absorbed fairly well. One dose of approximately 300 mg (the size of an aspirin tablet) keeps acting for about a week, as absorption continues along the intestine, and as it is "recycled" in the body. Part of this long lasting effect is because it improves the body's ability to produce its own pregnenolone.

### Source 3 — Ray Peat Email Advice Depository — Post 192

Ray Peat · Email · Jan 14, 2016

> **Question:** Dear Ray, I have been reading an article today on Dr Oram's research using a more sensitive c-peptide test on people with type one diabetes, which showed their beta cells still produce insulin even after many years (30+) of having the disease. I have recently read your articles also and the implications of DHEA on beta cell regeneration in rabbits. Is pregnenolone able to convert into DHEA in someone with type one diabetes if supplemented and potentially have the same effect as the DHEA? Any further reading or information greatly appreciated.
>
> **Ray Peat:** Pregnenolone does convert to either DHEA or progesterone . Sugar and brewer's yeast are other things that help with the regeneration. Keeping free fatty acids low is important, and niacinamide could help with that.

### Source 4 — Glossary

Ray Peat · Glossary

> Pregnenolone
>
> To produce pregnenolone, thyroid, vitamin A, and cholesterol have to be delivered to the mitochondria in the right proportion and sufficient quantity. Normally, stress is balanced by increased synthesis of pregnenolone, which improves the ability to cope with stress. Lipid peroxidation, resulting from the accumulation of unsaturated fatty acids, iron, and energy deficiency, damages the mitochondrias' ability to produce pregnenolone. When pregnenolone is inadequate, cortisol is over-produced. When progesterone is deficient, estrogen's effect is largely unopposed. When both thyroid and progesterone are deficient, even fat cells synthesize estrogen.

### Source 5 — Life Supporting Substances Its Rain Making Time 2011 07 04

Ray Peat · Interview · Jul 4, 2011 · http://l-i-g-h-t.com/files/rarinmaking-time-life-supporting-substances.mp4

> **Ray Peat:** I just sort of accidently discovered its value, and that started me reading about it. I had been experimenting how best to assimilate a supplement of progesterone and DHEA. So I was trying all of the steroids that I had at hand in different solvents, and vitamin E worked very well for DHEA and progesterone, but it didn't seem to dissolve very much of the pregnenolone. And so I had a bottle of vitamin E that I was using just to use it up as a supplement. And during a trip of a few weeks I started getting sick and went back and was so sick I was staying in bed for I guess a few weeks before it occurred to me that the only thing different on that trip was that I had not had my little bottle of vitamin E with me. And I thought, "Could it be that that E had retained some of the pregnenolone that I had stirred into it?" So I got up and took just a pinch of plain pregnenolone powder. In about 30 or 40 minutes all of my symptoms had disappeared. That was 1984. Since then the symptoms have never returned. For several years, every ten days I would take a good fat pinch of pregnenolone, maybe 300 mg. And one dose of it for me would last ten days before the symptoms would return. And I bought a kilogram to experiment with it, and to see what a big dose did, I would take 3,000 or 4,000 mg at a time.

### Source 6 — From PMS to Menopause: Female Hormones in Context

Ray Peat · Book · 1997

> **Ray Peat:** A tenth of a gram is a reasonable first dose, though some people seem to need as much as 1 gram per day, possibly because of poor absorption. (The amount produced daily in a healthy young adult is roughly 30 mg.) Normalizing the stress hormones with pregnenolone often seems to have the effect of correcting the function of the thyroid gland, probably because it is suppressed by stress. Since pregnenolone is the precursor for progesterone and DHEA (and all the other steroid hormones), it often has the same effects as progesterone or DHEA, and it has the advantage that it allows the body to produce just an optimum amount of those hormones. In very old people, or people with special enzyme deficiencies, it might be necessary to supplement all three to achieve their normal physiological concentration in the tissues. Pregnenolone and progesterone are known to protect nerves against the damaging effects of the "excitotoxins," which activate nerve cells to the point of cumulative injury during stress and fatigue. The need for pregnenolone is probably what is described as "agitated depression," in which the person feels unable to cope with ordinary life, and when the body is unable to produce enough pregnenolone, the nervous-physiological distress leads to increased production of cortisol. The clinical depression, which so typically involves elevated cortisol production, is probably primarily a pregnenolone deficiency. The active fraction of the thyroid hormone, triiodothyronine, or liothyronine (T3), is essential for the conversion of cholesterol to pregnenolone, as is the retinol form of vitamin A. Butyric acid is known to facilitate the entry of T3, into the mitochondrion. Since progesterone and pregnenolone protect against the excitotoxins which damage neurons, and estrogen and cortisol promote excitotoxic damage, it seems reasonable to see this opposition as relating to their known physiological actions.

### Source 7 — Your Own Health And Fitness: Thyroid/Progesterone And Diet

Ray Peat · Interview · Nov 12, 1996 · http://www.l-i-g-h-t.com/files/your-own-health-and-fitness-thyroid-progesterone-and-diet -november-12-1996-57-mins.mp4

> **Ray Peat:** The one hormonal effect that has been seen consistently and it’s the only thing that shows up in when you study animals or people who were given pregnenolone, the only hormonal consequence is that if their cortisone is elevated, pregnenolone brings it down to normal, that’s because the elevation of cortisol is connected through mechanisms in the brain circuitry. High cortisol is the symptom of a pregnenolone deficiency and once you get your cortisone down by having enough pregnenolone, then any amount of pregnenolone you take has no hormonal action whatsoever, but you need to be saturated otherwise you are going to resort to cortisone and cortisone is the basic thing that ages the skin, the brain cells, the bones. Every cell is aged faster under the influence of cortisone.
>
> **Layna Berman:** Okay. And then pregnenolone usually advice people after 50 to do. Incidentally just to let you know, I am going to go long on this interview. What I'll do is I’ll still break at 12:30 for about 30 seconds and you guys who are listening who want to call him, please try to maybe write to me your questions out because we’ll probably have to move quickly through the calls and then when we come back from break, I’m going to go ahead with the interview for maybe another 10 minutes because there is several things I want to sort of go through with Ray before I open up the phone lines, so start listing your questions down so we can move through them quickly. Pregnenolone after 50, now we’ve got vitamin companies are pushing DHEA, so why don’t you explain how that fits in.

### Source 8 — Generative Energy: Restoring the Wholeness of Life

Ray Peat · Book · 1994

> In 1944 factory workers were given daily doses of pregnenolone and, on alternate weeks, a placebo. During the pregnenolone weeks. their piece-work output was significantly higher. Healthy young people who are not under stress do not feel anything from taking even a very large dose (e.g., one gram). and no changes have been detected in blood glucose, proteins, amino acids. or salts. The urine apparently contains more conjugated steroids (indicated by an increased tendency to foam) after taking a large dose of pregnenolone; I think light is the main factor normally causing changes in the conjugated steroid content of urine. The skin and the brain are important sites of steroid synthesis, and they are usually ignored by endocrinologists investigating steroid hormones. Papa and Kligman (1965) showed that adding pregnenolone or progesterone topically to skin would restore youthful properties to aged skin. I think DHEA gives similar results, and (like progesterone) is more easily absorbed than pregnenolone. Both progesterone and pregnenolone seem to improve the efficiency of blood circulation. I have seen grey-skinned depressed people turn pink and start smiling shortly after taking pregnenolone. About 1950. pregnenolone was tested on several people with exophthalmia from Graves' disease. and it was reported that their eyes quickly receded toward a more normal position in their sockets. Having read this, I mentioned it to a desperate woman with horribly bulging eyes. Her left eyeball was about 50% exposed. and the other one was less extreme, but still seriously protuberant. She took some pregnenolone as we talked, and within an hour it seemed to me that her eyes were receding. An hour after she took the pregnenolone. she said her eyes were feeling much better. I left her city early the next morning, but she telephoned me the next day and claimed that her eyes were completely normal. Without seeing her, I don't know exactly what she meant by "normal." This happened over two years ago, and I hope to visit her city soon to see whether her eyes really became, and stayed, normal. For many years it has been known that steroids, including cholesterol, have an anti-toxic effect.

### Source 9 — Generative Energy: Restoring the Wholeness of Life

Ray Peat · Book · 1994

> [references]
>
> ### Chapter 11: Pregnenolone
>
> My interest in pregnenolone was the result of an accident. I had been experimenting with the solubility of various steroids. I found that pregnenolone isn't very soluble in vitamin E, and I saved the bottle containing vitamin E and pregnenolone to use as a vitamin E supplement. I had another bottle of pure vitamin E. In 1983, the ocean current called El Nino caused Oregon's weather to stay cloudy and rainy through the summer. I didn't have my usual summer recovery from "winter sickness," and by November I was becoming very sick. During a two week trip I felt perfectly well, but except for that short time I kept getting sicker and sicker (with inflammation of arteries, dental abscesses, asthma, migraines, and colitis). Lying in bed one day trying to understand what had happened during that twoweek trip, I remembered that I had used the vitamin E containing a residue of pregnenolone on the trip, but used pure vitamin E after I got home. I immediately got out of bed and took a pinch of pregnenolone. In about an hour, all of my symptoms had stopped, and for over a week I was healthy and energetic. But then I got sick again, and was so distracted by the pain that it was several days before I remembered the pregnenolone. Another pinch had the same dramatic sudden effect. Since then I have taken some almost every day. While I was sick I had pictures made for a passport, but they looked so odd that I got several more. The best of those, the least haggard looking, is reproduced here.
>
> Pregnenolone is known to be produced (in the mitochondria) from cholesterol. This is the first stage in the production of all of the steroid hormones. If pregnenolone synthesis is insufficient, supplementary pregnenolone would help to maintain an optimum level of the various other steroids. Aging, stress, depression, hypothyroidism, and exposure to toxins are conditions in which synthesis of pregnenolone might be inadequate.
>
> In 1944 factory workers were given daily doses of pregnenolone and, on alternate weeks, a placebo. During the pregnenolone weeks. their piece-work output was significantly higher.

### Source 10 — Your Own Health And Fitness: Thyroid/Progesterone And Diet

Ray Peat · Interview · Nov 12, 1996 · http://www.l-i-g-h-t.com/files/your-own-health-and-fitness-thyroid-progesterone-and-diet -november-12-1996-57-mins.mp4

> **Layna Berman:** That’s right.
>
> **Ray Peat:** Try the one that tends to kill you sooner.
>
> **Layna Berman:** That makes sense. So thyroid and pregnenolone first. That makes sense. You had success treating Graves' disease with pregnenolone? I mean they are eradiating people's thyroids for Graves.
>
> **Ray Peat:** Yeah. There is published stuff using what I consider mild doses of pregnenolone. All of their people, the eyes receded and in my few experiences the eyes just sort of were sucked back into the head. It’s such a dramatic process that you have to see what it can do to deformed arthritic joints or emphysema in which there is almost no oxygen getting through the lungs or in the state of Graves' disease in which there is a gelatinous material behind the eyeball. The valves of the heart can get the same gelatinous deposit which is, it historically is part of as low thyroid product, a glycoprotein but pregnenolone has the most dramatic almost instantaneous effect like in an hour you can see results.
>
> **Layna Berman:** Okay. What I want people to do is to make sure you got a pencil and paper because I want Ray to give out his PO BOX number and his address. I'm sorry his PO Box number and if you'd like to Ray, also you’re phone number in a second because you actually make an oil which is a vitamin E oil with progesterone which is much stronger than the creams that are available on the market and I think it's a very effective way of supplementing for progesterone and it's easily gotten by ordering it from you by mail including all of your books which are self-published and available by ordering them from you by mail, but you know why you never send a protocol with your progesterone oil, so I’m getting no end to phone calls.

### Source 11 — #82: What's More Toxic: PUFA or Endotoxin?  |  Euphoria  |  Addiction  |  Meaningful Work  |  Current Events

Ray Peat · Interview · Apr 30, 2022

> ## Pregnenolone and Progesterone
>
> **Ray Peat:** In the early 1950s, there were studies showing that it's much better than cortisone or cortisol for those uses—anti-inflammatory and so on. But its role in the system makes it even worse [for pharma] than progesterone. Progesterone cures essentially everything: trauma, all of the degenerative and stress-related diseases. It's hormonally more powerful than pregnenolone, but pregnenolone has the same position in the system. When you take other hormones, the body's production of that hormone decreases. But in the case of progesterone and pregnenolone, those substances support the body's production of more, up to their ability to make more. So if you're deficient in progesterone, sometimes a single dose or two can activate your body to return to normal production if you have the thyroid, vitamin A, and cholesterol needed. To a degree, the same situation exists with pregnenolone. It stabilizes the damaged mitochondria and makes it possible for your cells to organize energy production and more pregnenolone and progesterone production. The drug companies first realized that progesterone and DHEA were terrible drugs because they tend to cure diseases. The effects of pregnenolone—there are no recognized hormonal effects—but if you have enough of it, in experiments, a rat could be given 10 grams per dose with no harmful effects except to stop stress hormone production. Pregnenolone is a relatively expensive material if you supplement it adequately. But since it isn't patentable, those three steroids are something that could essentially cure most of the current diseases if they were made available massively and cheaply. That doesn't interest the drug companies because they don't have patents.

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