*Dr. Sahelian's View of Pregnenolone

© Ray Sahelian M.D.

What hormone?

Reduces stress
Provides a mild, calm, pleasant feeling
Improves energy, mental outlook and motivation
Increases mental acuity and awareness
Relieves arthritic aches and pains
Helps fight disease
Makes you feel younger and more vibrant
Pregnenolone (Preg for short) is a hormone that can improve the quality of life of a large segment of the population, but its potential has yet to be fully explored. Why is this?

Preg is a natural hormone which cannot be patented. Back in the 1940's, when researchers started experimenting with the use of Preg, they realized that it could be helpful for people under stress and it could increase energy in those who were fatigued. However, about the same time, cortisone, another closely related hormone, was discovered. Cortisone stole the limelight. When cortisone was given to individuals with rheumatoid arthritis, there were outstanding short-term improvements. Photographs of these remarkable recoveries were circulated and the medical community was impressed. Scientists basically put Preg aside to focus on cortisone. The structure of cortisone was altered to make similar molecules such as dexamethasone and prednisone, much more powerful steroids. Dexamethasone and other similar corticosteroids could be patented, and thus a pharmaceutical company could make a lot of money by owning the patents.

Preg has stayed in relative obscurity since the 1940's, with only rare mentions in the medical literature. A review of Medline, the computer system that records all articles published in scientific journals, shows only a few studies published on Preg in 1995 and 1996, and only a couple involve human subjects.

Since mid 1996, public attention has slowly refocused on Preg. Why? Because Preg has become more readily available to the consumer through mail order vitamin firms, health food stores and even some drug and retail stores. (The publication of DHEA: A Practical Guide, a 30 page booklet, in July of 1996 also played a role in heightening interest within the supplement industry.)

You may already know that melatonin, a hormone made by the pineal gland, is sold without a prescription. So is DHEA (dehydroepiandrosterone), a hormone made by the adrenal glands. How is it that hormones are now available without a prescription?

The Dietary Supplement Law of 1994
In October, 1994, a law was passed by Congress making it easier for companies and drug/vitamin stores to sell any vitamin, mineral, herb, nutrient, amino acid, food extract or any derivative of these supplements without FDA approval. As you can see from the diagram Preg is a derivative of cholesterol.

Cholesterol itself is derived from the foods we eat, such as meats, eggs, poultry, butter, and dairy products. Cholesterol is also produced by the body, especially the liver. Therefore, even though Preg is a steroid hormone, it is still considered a food derivative and thus does not fall under the jurisdiction of the FDA. The only certain way the FDA could pull this hormone off the market would be if there were reports of serious side effects. So far, there have been no serious side effects reported with this steroid.

What is a Steroid?
A steroid is any chemical substance with four carbon ring structures attached to each other. Cortisol, DHEA, testosterone, Preg, progesterone, and estrogen are all steroid hormones that chemically look very similar to each other. Structurally, they differ from each other in only small ways. However, even tiny changes in the chemical make up of a substance can make enormous differences in how it functions and what role it plays in the chemical factories of our bodies.

For instance, testosterone, the male hormone, is only slightly different chemically from estrogen, the female hormone. Yet that slight difference causes men to grow facial hair and women to develop breasts.

Many people think of the word steroid as a synthetic substance used by body builders and weight lifters to boost muscle mass. These types of synthetic steroids are called anabolic steroids and do influence muscle growth at the expense of potentially serious side effects. Preg and DHEA are not considered anabolic steroids since they have only a weak anabolic influence.

How is Preg Made?
There is a type of vegetable called a wild yam that is grown in certain parts of the southern U.S. and in Mexico. This wild yam contains a compound called Diosgenin that is the precursor to steroid hormones. In a laboratory, Diosgenin is converted into Preg. Further metabolism can convert Preg into DHEA.

The human body does not have the ability (the required enzymes) to convert Diosgenin into Preg. Therefore, if you swallow pills that are extracts of wild yams (Diosgenin), you will not get Preg or DHEA. The conversion of Diosgenin to Preg has to be done in a laboratory. If you want Preg or DHEA, the bottles you buy must say that they contain actual Preg or DHEA, not extracts of wild yams.

Where and How is Preg Made in the Body?
Preg is made in many organs and tissues that produce steroid hormones. The most common of these organs are the adrenal glands, liver, skin, and gonads (testicles and ovaries). Until 1981 scientists thought that steroids found in the brain came from elsewhere in the body. We now know that the brain has the capacity to use cholesterol to make Preg and other steroids (Warner, 1995). Preg is even made in the retina of our eyes (Guarneri, 1995).

There are enzymes in cells that convert cholesterol to Preg. Each of the tissues and organs in our body have a different activity of this enzyme and thus Preg is made in varying amounts in different parts of our body.

The parts of the cell where Preg is made are called mitochondria. These are tiny little enclosures within cells that digest and break down sugars, fats, and proteins. Mitochondria are the chemical factories of a cell, and also are the places wher e steroids are produced.

The amount of Preg made depend s on how much cholesterol is brought to the mitochondria. Cholesterol usually floats within the cell in tiny clumps. When the body needs Preg and other steroids, it brings the cholesterol to the mitochondria, which then break a few side chains from the cholesterol to turn it into Preg (Stocco, 1992).

What other Hormones does Preg Turn Into?
The chemical name for Preg is 3-alpha-hydroxy-5-beta-pregnen-20-one. You see why it's called Pregnenolone. Preg can be easily converted into DHEA which in turn is converted into androgens, estrogens and other steroids. As you can observe from the diagram on page 4, there's another pathway that Preg can take. It can be metabolized into progesterone which in turn can turn into aldosterone or corti-sol. This is what makes Preg different from DHEA. It has the ability to form other hormones such as progesterone. DHEA has often been called the "Mother hormone." I call Preg "The mother of DHEA, and Grandmother of all steroid hormones."

When you take Preg, your body will decide which pathway it will take. Will it go the DHEA way, or progesterone/cortisol/aldosterone direction?

Hans Selye, the well-known pioneer researcher on stress, was one of the first to point out Preg's ability to be converted into different steroids. Back in 1943 he wrote: Pregnenolone distinguishes itself from other steroids because it possesses so many different activities. Thus the compound possesses, at least in traces, every independent main pharmacological action which has hitherto been shown to be exhibited by any steroid hormone. In the light of these observations it was tempting to speculate on the possible role of the compound as an hormone-precursor from which the organism may, according to its needs, produce compounds in which one effect is particularly developed at the expense of other activities of the parent substance. One advantage that Preg has over DHEA is that it is less androgenic, that is, individuals who get acne or facial hair from DHEA would be much less likely to do so on Preg.

How Soon Will I Notice an Effect from Preg?
Most users who start with 10 mg will not feel an effect. When the dose is raised to 20 mg, some may feel a calm, energetic feeling. This becomes more pronounced when the dose is raised to 30 mg or higher. However, some individuals will not feel an effect even on 40 mg, 50, or higher doses.

You should be patient with Preg since, if you're taking a low dose, it sometimes takes up to two weeks or a month to notice the effects. On a high dose, some people may feel a difference even as soon as a few hours after taking it. The effect becomes more pronounced in late afternoon and evening.

What Time of Day Should I Take Preg?
I recommend that you take it first thing in the morning with breakfast since taking Preg later in the day can lead to insomnia.

Is it Okay if I Self-Medicate with Preg?
Your health care provider should be consulted anytime you plan to use hormone supplements for prolonged periods. After all, Preg is converted to progesterone, DHEA and androgens and estrogens. Taking Preg is not as simple as popping a vitamin C pill.

Is Preg Safe?
When mice were given up to 5 grams (g) of Preg per kilogram (kg) of body weight, no symptoms were produced (Henderson, 1950). One kilogram is 2.2 pounds so this would be equivalent to giving a 70 kg (154 pound) human 350 g. Most of the pills sold over-the-counter are less than 50 milligrams (mg). (Please note that 1 gram equals 1,000 milligrams.)

In a long-term study, mice were given 1 g of Preg per kg of body weight three times a week for 50 doses with no toxic reactions. No changes were noted in red blood cells, white blood cells, hemoglobin, or the weight of body organs. Also, no changes were found in food intake, growth rate, fertility, or the size and condition of their offspring.

In humans, when 25 men were given between 25 and 75 mg of Preg daily, one person developed a rash which stopped after the Preg was discontinued. None of the other users developed side effects.

In another study, when 8 patients received 50 to 150 mg of Preg daily by intramuscular injection, no adverse effects were noted. This study was continued for 75 days, and still no side effects were found.

Dr Gregory Pincus and Dr. Hudson Hoagland were even more confident about Preg's safety. Back in 1944 they wrote:

We should like to point out that we have encountered no deleterious result in connection with the ingestion of pregnenolone in our studies involving several hundred men and women who have taken the medication; in some instances in doses of 100 mg per day for as long as four months. The substance [Preg] is nontoxic.

For the most part, persons report no subjective experiences after its ingestion, although a considerable number have insisted that they experience a general feeling of well being and that they tire less easily when taking it."

Dr. Eugene Roberts, of the Department of Biochemistry, Beckman Research Institute of the City of Hope, Duarte, California, and perhaps the world's foremost researcher on Preg, reports in his 1995 article that 525 mg of Preg given daily to patients with Alzheimer's disease for 3 months did not induce any toxicity.

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