Pregnenolone
Pregnenolone the parent (precursor) hormone from which
all other vital male and female hormones are made, has
been studied for its effects on health, longevity, and
emotional well-being sense the 1940's. Pregnenolone is
made from cholesterol in the body. It can be
synthesized into a number of hormones - estrogen,
progesterone, testosterone, DHEA, aldosterone, cortisol,
etc. It is, in fact, the master hormone from which all
the steroid hormones are derived.
Made from cholesterol, pregnenolone is a natural steroid
hormone produced primarily in the adrenal glands, but in
smaller amounts by many other organs and tissues of the
human body, including liver, brain, skin, gonads, and
even the retina of the eye.
Your adrenal glands are responsible for manufacturing
DHEA. Actually, the cascade
of adrenal hormones starts with cholesterol, from which
the brain hormone pregnenolone.
Pregnenolone is then transformed into DHEA. And DHEA
serves as the raw material from which all other
important adrenal hormones--including the sex hormones
estrogen, progesterone, and testosterone and the stress
hormone cortisol--are synthesized. DHEA is the most
abundant hormone in your body. But production peaks at
around age 20. From then on, your DHEA level decreases
with age. By the time you reach 40, your body makes
about half as much DHEA as it used to. By 65, output
drops to 10 to 20 percent of optimum; by age 80, it
plummets to less than 5 percent of optimum.
Pregnenolone declines in the body more than 60 percent
between the ages of 35 and 75. Along with this natural
bodily decline, our bodies have had to deal with a
decrease in the building block of pregnenolone.
Memory Aging and Autoimmune Diseases
Pregnenolone's as the precursor of all hormones is at
the very top of the hormone heap confers upon it unique
powers. As the ultimate precursor, ready and willing to
be converted to any of more than 150 adrenal steroids,
pregnenolone can participate in every biochemical action
that every steroid hormone is party to. Thus,
pregnenolone influences cerebral function, energy level,
the female reproductive cycle, immune defenses,
inflammation, mood, skin health, sleep patterns, stress
tolerance, wound healing, and much, much more. This is
one hormone that knows where the action is and loves to
take part. As with DHEA and other anti-aging hormones,
the production of pregnenolone declines with age.
Research will almost certainly prove that pregnenolone
replacement therapy can slow the aging process. Many
scientists and doctors believe that restoring
pregnenolone to youthful levels is a powerful anti-aging
strategy for both body and brain. Pregnenolone
supplementation is natural and physically harmonious,
according to Eugene Roberts, Ph.D., a neurobiologist at
the City of Hope Medical Center in Los Angeles. Because
of the hormone's role as a precursor, pregnenolone has
the unique ability to bring all of the other hormones
into balance. It stimulates production of those other
hormones, but only when they are needed. Taking
pregnenolone therefore normalizes and rejuvenates the
entire adrenal system.
Pregnenolone has been shown to enhance several aspects
of neurological functioning, including cognitive
benefits such as enhancing learning and memory, and
motor-nerve effects such as improved psychomotor
performance. Pregnenolone has been used to benefit
connective tissue disorders such as lupus and
autoimmune/rheumatoid arthritis. As a neurohormone,
pregnenolone has a powerful effect on improving
transmission of nerve impulses, which may enhance memory
relay pathways. Pregnenolone may allow skin cells to
contract, restoring firmness to slack skin. Pregnenolone
has been able to quickly cause other rapid anatomical
changes which may be from eliminating edema (water
retention), such as helping protruding eyes (as in
Graves' disease) to recede, or helping joint cartilage
to function normally without pain, or causing lungs to
oxygenate the blood more efficiently in people with
emphysema.
Hormone Replacement Therapy
Menopause is a dreaded ordeal for the millions of women
who choose not to use estrogen replacement therapy
because of a four to eight tines higher chance of
uterine cancer. The pharmaceutical companies developed
'hormone replacement therapy," which combines synthetic
progesterone with conjugated equine estrogen. The
majority of female consumers of this therapy are
probably unaware that the estrogen they are taking is
not natural to the human body and comes from a pregnant
mare's urine (PMU). Dr. John R. Lee notes that 52
percent of the estrogens in this concoction are the
horse estrogens equilin and equilenin, which are not
natural to humans.
Doesn't it make more sense to use a natural substance in
hormone replacement therapy? The best thing about
pregnenolone is that is it is completely natural. The
human body, the true "master chemist," transforms
pregnenolone into the hormones the body is lacking.
Whether its estrogen, progesterone or testosterone,
using pregnenolone, the wisdom of the body makes what is
needed most.
Anti-arthritis Effects
During the 1940s, pregnenolone was used successfully as
a treatment for rheumatoid arthritis. A 1950 review
article on pregnenolone reported on a study by Henderson
and colleagues who found that 300 mg pregnenolone/day
for 40 days resulted in a significant decrease in joint
pain, tenderness, and spasticity, with improved strength
and range of motion. Another study by Freeman and
colleagues, with 64 patients, used 500 mg of
pregnenolone daily for periods of 2 to 30 weeks. 24
patients showed striking improvements, and 20 showed
minor improvements.
Unfortunately, the advent of the 'wonder drug' cortisone
(Cortisol) in the 1950s caused pregnenolone to be passed
by for arthritis treatment, since pregnenolone's results
were slower to manifest. Coincidentally, pregnenolone
could not be patented by the drug companies whereas
synthetic variants of cortisone could be (and were)
patented. By the time the nightmarish side-effects of
excessive cortisone were widely known by the medical
community in the 1960s (these side effects could include
psychotic breakdown, adrenal failure, and even death),
pregnenolone had been completely forgotten.
Stress
Like its daughter DHEA,
pregnenolone blocks
and reverses all of the age-accelerating effects of
excess cortisol. Cortisol, you recall, is a pro-aging
hormone. (It is also a granddaughter of
pregnenolone and the
only adrenal steroid hormone that increases with
age.) Normally the adrenal glands produce small
amounts of cortisol to protect you from stress. This
is okay, at least in the short run. Prolonged
overproduction of cortisol brought on by excessive,
unrelenting stress, however, causes an array of damaging
effects: brain dysfunction, accelerated skin aging,
impaired wound healing, excess fluid retention,
depression, and poor sleep quality. All of these shift
the aging process into overdrive. Pregnenolone also
protects you against chemical stress. Your liver
contains enzyme systems that are responsible for
removing toxins from your body. By protecting these
enzymes from cortisol, which degrades them,
pregnenolone
reinforces your body's detox power.
Dosage
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. Thus,
although pregnenolone appears amazingly safe and
beneficial, there are still many unanswered questions
regarding proper dosage, metabolism, and clinical
effects. Keeping these uncertainties in mind, here are
some recommendations for dosage.
For those wishing to err on the side of caution, 25 to
50 mg pregnenolone per day would probably be suitable
for use without physician monitoring. Perhaps an
additional safety margin (for this already
amazingly-safe substance) could be achieved through
discontinuing use for one week every month. Those
wishing to use the higher, anti-arthritis doses (200 -
500 mg/day) should probably do so only under the
supervision of their physician, even though many human
clinical studies with arthritis at these dosages yielded
no problems or toxicities. 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). On an anecdotal note,
there have been patients taking 100 - 1,000 mg
pregnenolone/day intermittently since 1987, with no
discernible negative side effects.
Safety Studies
Fortunately, pregnenolone is amazingly safer than other
steroids. Pregnenolone researchers working with both
human and animal subjects since the 1940s have
consistently commented on pregnenolone's 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, eight people received 50 to 150
milligrams per day by intramuscular injection for 75
days, with no reported side effects. Dr. Eugene Roberts
gave 20 Alzheimer 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.
Consult with a physician before using any nutritional
supplement
Caution:
Pregnenolone should be avoided by children, pregnant
women and nursing mothers. Do not use pregnenolone if
you are supplementing DHEA. Do not use if you suffer
from seizure disorders, as pregnenolone can suppress
GABA activity, resulting in an increase in central
nervous system activity, which may lead to seizures in
those with epilepsy. Men with prostate cancer, or
high PSA levels (which may be worsened by testosterone)
and women with breast or ovarian cancer (which may be
worsened by estrogen) should probably take pregnenolone
only with their doctor's consent and supervision. On
no account use pregnenolone instead of medically
prescribed steroids, without telling your doctor what
you are doing.
Sources:
Pregnenolone: Nature's Feel Good Hormone. Sahelian, Ray,
M.D. (Garden City Park, New York: Avery Publishing
Group, 1997), 57.
Pregnenolone - Master Hormone for Women ...and Men!, D.
Gary Young, Reprinted from Essential Edge Magazine,
Fall, 2000
Pregnenolone:
The Superhormone for Your Brain [material on Dr. R. Sih]
in The Superhormone Promise, Regelson, W. and Colman,
C. Simon and Schuster, 1996.
Henderson, E., et al. Pregnenolone. J Clin Endocrinol
10: 455-74, 1950
Pregnenolonefrom Selye to Alzheimer and a model of the
pregnenolone sulfate binding site on the GABA-A
receptor. Roberts E. Biochem Pharmacol 49: 1-16, 1995.
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