Pregnenolne: the Queen of the Adrenal Hormones
A Gem for Health Protection and Healthy Aging
As the body’s supply of pregnenolone diminishes, so does the availability of its other related hormones. This has led scientists to consider pregnenolone supplementation as a way to turn back the clock on aging and counter the consequences of this dramatic drop in hormone levels.
‘Pregnenolone, which is the raw material for producing many of the hormones of stress and adaptation, was known as early as 1934, but for several years it was considered to be an "inert" substance. A reason for this belief is that it was first tested on healthy young animals. Since these animals were already producing large amounts of pregnenolone (in the brain, adrenal glands, and gonads), additional pregnenolone had no effect. In the 1940s, pregnenolone was tested in people who were sick or under stress, and it was found to have a wide range of beneficial actions, but the drug industry never had much interest in it. It’s very generality made it seem unlike a drug, and its natural occurrence made it impossible to patent. Thus, many synthetic variants, each with a more specialized action and some serious side effects, came to be patented and promoted for use in treating specific conditions. The drug companies created an atmosphere in which many people felt that each disease should have a drug, and each drug, a disease. The side effects of some of those synthetic hormones were so awful that many people came to fear them. For example, large doses of synthetic varieties of "cortisone" can destroy immunity, and can cause osteoporosis, diabetes, and rapid aging, with loss of pigment in the skin and hair, and extreme thinning of the skin. Natural pregnenolone is present in young people of both sexes at a very high concentration, and one reason for the large amount produced in youth is that it is one of our basic defences against the harmful side effects that an imbalance of even our natural hormones can produce. In excess, natural cortisone or estrogen can be dangerous, but when there is an abundance of pregnenolone, their side effects are prevented or minimized. In a healthy young person or animal, taking even a large dose of pregnenolone has no hormone-like or drug-like action at all. It is unique in this way. But if the animal or person is under stress, and producing more cortisone than usual, taking pregnenolone causes the cortisone to come down to the normal level. After the age of 40 or 45, it seems that everyone lives in a state of continuous "stress," just as a normal part of aging. 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 tumours that can be caused by estrogen. Pregnenolone is largely converted into two other "youth-associated" 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. It tends to improve function of the thyroid and other glands, and this "normalizing" effect on the other glands helps to account for its wide range of beneficial effects’
Raymond Peat, MA, PhD (Univ. of Oregon) Endocrine Physiologist, specializing in hormonal changes in stress and aging
Discovered in 1940s, pregnenolone came into prominence only recently with its major stress and pain relieving properties for men and women suffering from different inflammatory and stress related conditions of the mind and body. Pregnenolone is one of the most effective and powerful and yet one of the most overlooked hormones with a multitude of different health benefits for both men and women.
Pregnenolone is the source of the production of all other important steroid hormones in the body such as progesterone, DHEA, mineral corticoids (which regulate electrolyte balance), corticosteroids (which influence inflammation and metabolism), estrogens, and androgens. As pregnenolone is the precursor and controller of all these essential hormones in the body, it can be helpful in the treatment of a variety of conditions such as arthritis, cancer, osteoporosis, obesity, multiple sclerosis, premenstrual syndrome, and menopause.
Pregnenolone thus offers great hope for men and women suffering from the above conditions of the mind and body. Other than these conditions, pregnenolone has also been found helpful in certain peculiar conditions affecting men and women. Pregnenolone interlinking role with other reproductive and steroid hormones in the body like DHEA, testosterone, progesterone and estrogen makes pregenelone benefits effective in treating various anti ageing conditions like menopause in women.
Pregnenolone may be one of the most important hormones because it seems to have a balancing effect. It is a precursor to many other hormones and may be able to bring the levels of other hormones up or down as needed.
Other benefits of pregnenolone may include stress reduction and increased resistance to the effects of stress, improvement of mood and energy, reduced symptoms of PMS and menopause, improved immunity, and repair of myelin sheaths.
Pregnenolone also operates as a powerful neurosteroid in the brain, modulating the transmission of messages from neuron to neuron and strongly influencing learning and memory processes. As with DHEA, pregnenolone levels naturally peak during youth and begin a long, slow decline with age. By the age of 75 our bodies produce 60% less pregnenolone than the levels produced in our mid-thirties. For this reason pregnenolone is one of the biomarkers of aging. Like counting the rings of a tree, by measuring the level of pregnenolone at any given point of a person’s life, it is often possible to make an educated guess as to his or her age.
Pregnenolone and the Nervous System
Pregeneolone is not only the ultimate mother hormone for all the adrenal (cortex) hormones, it is also an important nutrient for optimal function and repair of the nervous system, this is why it is sometimes referred to as a neuro-hormone. The brain and spinal cord contain higher concentrations of pregnenolone than anywhere in the body. Supplementing with pregnenolone can considerably improve memory, problem solving, mental dexterity and mood, especially in stressful situations.
Pregnenolone may help restore impaired memory, according to neurobiologist Eugene Roberts of the City of Hope Medical Center in Los Angeles, and his colleagues, biologists James F. Flood and John E. Morley, of the St. Louis VA Medical Center. These researchers tested pregnenolone and other hormones on mice. They found that pregnenolone is several hundred times more potent than any memory enhancer that has been tested before. Their report, in the March 1992 Proceedings of the National Academy of Sciences, says that pregnenolone restores normal levels of memory hormones which decline during aging.
For diseases involving the nervous system: Pregnenolone and its sulfate belong to the group of neurosteroids that are found in high concentrations in certain areas of the brain, and are synthesized there. Neurosteroids affect synaptic functioning, are neuroprotective, and enhance myelinization. Pregnenolone and its sulfate ester are under investigation for their potential to improve cognitive and memory functioning. Pregnenolone can be helpful in preventing or alleviating mental diseases of old age such as Alzheimer’s disease. It can also help to repair and maintain the myelin sheaf, making it a prime remedy as part of a healing regime for Multiple Sclerosis. Pregnenolone has even been shown to help healing of spinal cord injuries especially if given soon after the injury. Pregnenolone has anti-inflammatory effects. When it was administered immediately after a spinal cord injury, it reduced histopathological changes, spared tissue, and aided the restoration of motor function. (Victoria Dolby. Pregnenolone (Kindle Locations 132-137). Kindle Edition.)
Pregnenolone; other benefits on mental and emotional function and accomplishing tasks.
A study of aviators found that pregnenolone improved their functioning and perception of their work. Fourteen subjects took 50 mg of pregnenolone daily and performed tests with an automatic scoring device that operated like the joystick for a video game. Researchers found that the improvements the aviators experienced during the two weeks of administration had a cumulative effect that continued for several days afterward.
In another experiment, 25-75 mg of pregnenolone were given daily to 8 leather cutters, 12 lathe operators, and 77 optical workers. While there was little benefit compared to placebo when the workers were not under pressure, productivity rose when the level of work-related stress was higher. Once again, the effect outlasted the length of the study. The subjects also felt that they tired less easily and were better able to cope with the demands of their jobs. No side effects were reported in any of these studies.
in the book Pregnenolone: A Radical New Approach to Health, Longevity, and Emotional Well-Being, author Dr. Gary Young, N.D., points out that pregnenolone enhances mental performance, facilitates learning, helps the body adapt to stress, increases one’s overall feeling of happiness and well-being, and helps induce a change of attitude in which we actually become more appreciative of life.
Relief of anxiety and panic attacks: A deficiency of pregnenolone turns on an anxiety-producing substance (endozepine), which triggers anxiety and panic attacks.
Pregnenolone and diabetes
‘Pregnenolone therapy is recommended for all diabetics past the age of 40 and is sometimes appropriate for younger patients. Pregnenolone was shown to rejuvenate the beta cells of the pancreas in diabetic animals and could be very helpful in humans as well.’ Victoria Dolby
Guardian of the Hormonal system
The several adrenal hormones produced by the adrenal cortex are produced one from the other thus: The main starting compound is cholesterol (Note: cholesterol is an essential nutrient and low cholesterol diets and especially cholesterol lowering drugs are simply bad for the health and have no cardio-vascular disease protecting effect see The Cholesterol Myth
The ‘mother’ hormone pregnenolone is produced from cholesterol, this is converted to DHEA and progesterone. Progesterone helps produce cortisol (hydrocortisone). DHEA converts to Androstenedione and this in turn can help produce both cortisol and testosterone, and eostrogen. The production of cortisone and other adrenal cortex hormones are mediated by the secretion of ACTH from the Pituitary gland in the centre of the brain. If this chain of events with its complex feedback mechanisms does not operate efficiently at any stage then hormone imbalance occurs, usually insufficiency. Therefore, the reasons for a DHEA, cortisol, testosterone or progesterone insufficiency can vary from person to person. Boosting the mother hormone pregnenolone can achieve raising of DHEA, cortisol, progesterone and testosterone levels sufficiently to overcome an insufficiency of those hormones. If all these hormones are raised to a level of a younger person great health benefits will ensue including a boost in well-being and general health into the older years and most likely, life extension. One may consider using pregnenolone instead of DHEA, however if you have identified a need for DHEA then whilst it is true that pregnenolone can help with overall adrenal integrity and balance of hormones in addition to the neuro hormone aspect it cannot guarantee production of the full amounts to restore youthful levels of DHEA, and so in these cases DHEA supplementation is still recommended alongside pregnenolone.
As the effects of pregnenolone are balancing on the other hormones in the adrenal hormone tree and also as its direct effects and ‘knock on’ hormone effects are so wide ranging it is logical that it will take longer to see the full regeneration effects and health protective effects of pregenolone than it would with a specific hormone further down the hormone tree. For example; cortisol insufficiency due to adrenal fatigue will be relived in hours with the correct dose of bio-identical hydrocortisone (cortisol) but could be resolved more holistically with pregnenolone. However it could take months for the adrenal glands to be restored with pregnenolone to be able to produce adequate cortisol on demand.
The fact that this can occur is exciting as it does indeed suggest that at least in some cases the entire adrenal hormone tree can be improved with just the use of pregnenolone. Individuals have reported fantastic health regeneration and apparent anti-aging effects. There is also evidence that the follow on hormones such as cortisol, testosterone, near the end of the hormonal tree have been boosted by pregnenolone supplementation. It seems apparent from the anecdotal reports that it is the higher doses of at least 50mg daily that have the most benefits in this area.
Pregnenolone and the Brain
Pregnenolone is able to reduce the activity of a receptor complex known as GABA. GABA is a neurotransmitter that literally cools the brain, protecting the nerve cells from burning out from all their activity. Too much GABA, however, can depress brain function, making the brain sluggish. By altering the extent of GABA-induced changes in membrane permeability, pregnenolone is able to reduce the increase in GABA transmission that occurs normally in older individuals. This counteracts the aging brain’s decline in mental sharpness.
Pregnenolone also promotes greater growth of brain cells. A recent study revealed that pregnenolone counteracted the usual age-related decline in neurogenesis in the hippocampuses of rats. The researchers found a 55% increase in cell proliferation in the dentate gyrus, where newborn cells differentiate into neurons. This effect continued for several weeks after a single infusion, suggesting that long-lasting benefits could be achieved from ongoing supplementation. Of course, the more brain cells you have, the more memories you are likely to retain.
An interesting article; Recharge With Pregnenolone
by Dave Tuttle, discusses the role of pregneolone in counteracting depression, fighting fatigue and boosting memory. It further relates to help for spinal cord injuries and rheumatoid arthritis.
In a recent Life Extension Foundation article titled "Enhancing Cognitive Function With Pregnenolone,” Dr. Julius G. Goepp, MD wrote:
"There is strong evidence that pregnenolone levels diminish with advancing age and that restoring these levels may help alleviate deteriorating brain function…This is borne out in research that has demonstrated pregnenolone’s ability to reduce the risk of dementia and improve memory, while also alleviating anxiety and fighting depression…Pregnenolone may play a pivotal role both in laying down memories in the first place, and then preventing their loss by directly protecting the nerve networks that store them! These complementary and versatile actions of pregnenolone are sending shock waves of interest through the scientific community because of the enormous implications for treating all sorts of age-related disorders of memory”
Dr. Goepp also points out, "Even more remarkably, from a treatment standpoint, researchers have shown that pregnenolone increases brain levels of acetylcholine, a key neurotransmitter required for optimal brain function, which becomes deficient in patients with Alzheimer’s disease. Acetylcholine is not only vital for thought and memory, it is also involved in controlling sleep cycles, especially the phase of sleep that is associated with memory (called paradoxical sleep or the random eye movement [REM] phase). Scientists have used this knowledge to study the effects of pregnenolone on sleep cycles and discovered that it dramatically increases memory-enhancing sleep. Together with previous findings that pregnenolone increases nerve cell growth (neurogenesis), researchers have concluded that pregnenolone can improve cognitive function in older animals by increasing acetylcholine levels, which stimulate new nerve cell growth in the brain areas most closely associated with memory and learning.”
Pregnenolone also appears to help people approach life’s daily challenges with a more positive mental outlook. According to the respected biologist and author Dr. Ray Peat, PhD, "When using pregnenolone, men and women alike report feeling a profound mood of resilience and an increased ability to confront challenges successfully.”
Dr. William Regelson, a respected pregnenolone expert and author of The Superhormone Promise: Nature’s Antidote to Aging writes that there appears to be a direct correlation between pregnenolone levels in the human body and emotional well-being. He states, "A recent study conducted by the National Institutes of Mental Health showed that people with clinical depression have lower than normal amounts of pregnenolone in their cerebral spinal fluid (the fluid that literally bathes the brain)." In other words, as pregnenolone levels decline, your emotional well-being can also sink like a stone.
Fortunately, pregnenolone is safer than other steroids. Pregnenolone researchers working with both human and animal subjects since the 1940s have consistently commented on pregnenolones virtual absence of toxicity. For example, the classic review article on pregnenolone by Henderson and colleagues in 1950 states: 'It [pregnenolone] has an extremely low order of toxicity; [it] has not shown any adverse effects on endocrine [hormone] physiology ....'
Pregnenolone has been given orally to humans at doses as high as 500 mg/day for as long as 30 weeks without evidence of adverse effects. Mice given 5 grams (1/6 ounce) per kilogram (2.2 pounds) of body weight suffered no ill effects. This would be equivalent to a 154 pound (70 kilogram) human ingesting 350 grams (approximately 3/4 pound) per day! In a long-term study, mice that were given one gram pregnenolone per kilogram of body weight three times weekly for 50 doses suffered no toxic reactions -- including no changes in the size and condition of offspring produced after the 50 doses.
In one human study, Dr. Eugene Roberts gave 20 Alzheimers patients 525 mg/day for three months with no toxicity. During rheumatoid arthritis experiments with pregnenolone, Dr. H. Freeman and colleagues gave 500 mg pregnenolone/day for up to 30 weeks, with no toxicity. And Drs. Pincus and Hoagland, two of the pioneer researchers on pregnenolone use by humans in the 1940s, found no toxic reactions with pregnenolone used by hundreds of men and women at dosages of 100 mg/day for four months. On an anecdotal note, there have been patients taking 100 - 1,000 mg (1gram) pregnenolone/day intermittently since 1987, with no discernible negative side effects.
Levels of pregnenolone are much higher in the developing embryo and at various stages of childhood. As very large doses of pregnenolone have consistently proved to be non-toxic without side effects the body obviously uses what it needs and ignores any excess. This gives a rationale for doses that Peat used e.g. 100 mgs or more daily, so that maximum benefits can be obtained in health regeneration. Also the process of therapeutic regeneration using a variety of supplements and methods does have at times a stressful effect on the body e.g. via detoxification and it is during these times that the body is in need of the buffering anti-stress effects of pregnenolone and the hormones it helps to produce such as progesterone, cortisol and DHEA.
The classic studies on pregnenolone and stress in the 1940s by Pincus and Hoagland generally used only 50 mg/day to achieve excellent results, while arthritis studies typically used 200-500 mg daily.
For those wishing to err on the side of caution, 50 to 100 mg pregnenolone per day would probably be suitable for use without physician monitoring. Morning is the perfect time to take pregnenolone, and a single daily dose is probably best, since pregnenolone is fat-soluble, and probably follows the circadian highs and lows of DHEA and cortisol (highest in the morning, with a drop to baseline by late afternoon).
Other dose considerations
Any nutritional supplement that improves the overall metabolic activity and efficiency to any significant degree is going to wake up the physiology. In this situation a multitude of nutrients are called into increasing play. If a person is deficient in electrolyte minerals especially and commonly unrefined salt (such as Celtic Ocean Sea Salt
), and also dehydrated and not drinking enough pure water, there can be adaption difficulties that could result in stress or insomnia or even palpitations for example. It is wise to always take adequate unrefined salt (at least 6 gram daily) and typically a minimum of 2 litres of water daily. This will give the body the best buffer to adapt to the uprating of the entire system that will be engendered by taking pregenolone. For salt /water deficient individuals even a dose as low as 10 mg pregenolone daily could create a stressful adaption situation. Also individuals with adrenal fatigue or insufficiency, generally would be advised to supplement with Adrenal MAX Support
(bio-identical hydrocortisone) first. The reason for this is that these individuals cannot tolerate much shifting into higher gear/ improved metabolic efficiency as cortisol /hydrocortisone in sufficient quantities is required to adapt to any significant change. Pregneolone will, over a sufficient period of time in some individuals (It may be most, we just don’t know at this stage) enable the adrenal glands to recover from a deficient state and produce the needed cortisol on demand, however this may take weeks or months and in the meantime the stimulation engendered may create adaption stress for those who are markedly adrenal incompetent as far as cortisone output is concerned. This may include aggravation of any pre-existent auto-immune disease. However, provided sufficient salt and water is taken even most adrenal fatigued subjects can adapt if starting at low doses e.g. 5 mg daily and gradually increasing the dose at a rate to suit the accommodation abilities of the individual, possibly aiming to reach at least 50 mg daily.