Hormonal Longevity Factor
Factor Four: DHEA-Forte
Factor Four: DHEA-Forte is a pharmaceutical-grade, pure
dehydroepiandrosterone, a precursor
considered to be a key biomarker in determining
biological age in both sexes.
Each vial contains 60 tablets of 25
mg pure DHEA
TO CONSIDER (OVERVIEW)
and Women over 40 years of age.
with low DHEA blood serum levels.
following menopause and/or hysterectomy.
exhibiting a family history of cardiovascular disease.
whose diet is high in refined carbohydrates.
desiring to boost their immune system.
on oral and vaginal contraceptives.
DOSAGE & DIRECTIONS
Men 40 to 55: Take one tablet daily with food on a
Men over 55: Take two tablets daily with food on a
Women over 40 or on contraceptives: Take one tablet
daily with food on a consistent basis.
Individuals with low DHEA: Take two to three tablets
daily until normal DHEA level has been achieved; then reduce
dosage to one tablet or follow age guidelines above.
Women in post menopause or surgical menopause: Take two
tablets daily with food on a consistent basis.
(dehydroepiandrosterone) is considered to be a key biomarker
in determining biological age in both sexes. DHEA, produced
by the adrenal glands, is the only hormone that peaks early
in life and starts to fall significantly thereafter, reaching
a low by the age of sixty.
does not have a "feedback" mechanism so supplementation
will not curb the body's production of this hormone.
CONTRAINDICATIONS & PRECAUTIONS
women, high dosage levels of DHEA can result in hirsutism
(excess body hair), fatigue, anger, depression, and acne rash.
High dosage levels for prolonged periods may stimulate breast
cysts or uterine fibroids.
In men, high dosage levels of DHEA may contribute to prostatic
hypertrophy, low energy, and aggressive anger.
The dosage levels recommended in this report are well within
safety tolerances and guidelines for normal DHEA usage.
However, never take supplements at the same time as medications.
If both must be taken with food, take them at different meals.
The following substances have been determined to lower DHEA
levels: corticosteroids, progesterone and other oral contraceptives,
cimetidine (Tagamet), lovastatin (Mevacor), ketoconazole (Nizoral),
anticonvulsants, carbamazepine, phenobarbitals, and alcohol.
is important to note that significant amounts of DHEA are
made only by humans and primates. Rodents, such as mice or
rats, have little circulating DHEA in their blood so any dose
given them would be a pharmacological dose.
Unfortunately, most studies involving DHEA have been conducted
with rodents and many of the "miracle" claims being
touted for DHEA have been based upon rodent studies. Much
of the extrapolation from rodent studies to humans may be
contradictory and, in fact, some of it has been proven to
The information and recommendations provided within this report
have been based upon the latest studies conducted on human
Recent research has found that DHEA supplementation in women
increases natural levels of progesterone and ameliorates hot
flashes. Only in women, in marked contrast with other mammals,
can the ovaries be removed without a predictable reduction
of sexual desire. From this, researchers have concluded that
human female sexual desire has shifted somewhat from estrogens
to androgens like DHEA, and from the ovaries to the adrenals.29
DHEA is a steroid hormone produced by the adrenal glands in
both men and women.7 This hormone is considered
a key biomarker in determining biological age as it cycles
on a life scale in both sexes. It is the only hormone that
peaks early in life and starts to fall significantly thereafer.8
DHEA is highest during the years of top physical condition,
rising rapidly just before puberty, then spiking between ages
twenty and twenty-five. It begins declining progressively
from that point forward, reaching a low by the age of sixty
and then slowly descends to less than five percent of peak
adult levels after age 70.9
The clear drop in men past forty is in sharp contrast to testosterone,
which declines noticeably in men only after age sixty.10
During the peak years between 25 and 30, men are believed
to make 1 to 2 mg of DHEA and 10 to 15 mg of DHEAS per day,
with women making somewhat lower amounts.11
It is believed that approximately half of the androgen and
estrogen precursors in the human body comes from the adrenal
glands' production of DHEA.12 As a result, the
decline in DHEA production by the body reflects itself in
Based upon the foregoing, it has been suggested that supplementation
with DHEA for those individuals 40 and older, bringing their
levels back to those of youth, could extend longevity and
improve the quality of life.
This suggestion gains further support in that DHEA, unlike
other steroids, does not appear to be regulated by a "feed-
back loop". DHEA supplements -except in very high dosages-
are not likely to stop the body's own production.13
There are many autoimmune conditions of which systemic lupus
erythematosus (SLE) is four times as common in women as in
men. Symptoms include painful swollen joints, skin rash, and
SLE is more common than previously thought. A study in England
found that 200 women out of 100,000 reported symptoms indicative
of the illness.14
A team of medical researchers from Japan determined that patients
with SLE had low DHEA activity.15
Physicians at Stanford University Medical Center conducted
a study with ten female patients with mild to moderate SLE.
The subjects were given 200 mg of DHEA daily for 6 months.
Following DHEA therapy, most of the symptoms were improved.
The researchers concluded: DHEA shows promise as a new therapeutic
agent for the treatment of mild to moderate SLE.16
It is believed that DHEA therapy could benefit other auto-immunity
diseases such as rheumatoid arthritis and multiple sclerosis.
However, the studies on lupus have been the only well-controlled
ones thus far. Further studies are clearly warranted.
Researchers from the
San Diego Medical School
evaluated 13 men and 17 women who ranged in age from 40 to
70 years. In a placebo-controlled, cross-over trail, they
provided 50 mg of DHEA nightly for 3 months.
Within two weeks, the DHEAS levels in the bloodstreams of
those receiving supplements reached those found in young adults.
The researchers concluded:
DHEA supplementation resulted in an increase in perceived
physical and psychological well-being for both men and women.
The subjects reported increased energy, a better mood, and
an improved ability to deal with stressful situations.17
DHEA has also been found to have a positive effect on memory.
When 500 mg of DHEA was administered to subjects an hour before
bed, there was a significant increase in recorded REM (dream)
sleep for two hours afterward. Dreams are thought to facilitate
The majority of the research evaluating the role of DHEA in
cancer has been done on rodents. Very little is known about
its role in cancer prevention in humans.
As stated earlier in this report, the results of experiments
involving rodents can be very different from results of similar
studies with human subjects, especially since very little
DHEA is found in the bloodstream of rodents.
DHEA levels can predict which women will get breast cancer
up to nine years in advance,19 and this steroid
actually counteracts a well-known cancer-causing substance
known as 12-0- tetradecanoyl-phorbol-13-acetate.20
Whether long-term DHEA therapy will help prevent cancer in
humans is undetermined at this time.
As humans age, the tissues develop a resistance to insulin
and the glucose remains in the blood at a higher level. In
a recent study 50 mg of DHEA was given daily for three weeks
to 11 postmenopausal women.21 The levels of triglycerides
declined and DHEA enhanced tissue insulin sensitivity.
Another study also confirmed significant improvement in insulin
sensitivity.22 The researchers concluded: DHEA
replacement may help attenuate age-related increases in insulin
It appears probable that DHEA has a positive effect in type
II adult onset diabetes.
Heart Disease (CVD)
A study involving 49 males younger than age 56 who were survivors
of a heart attack were compared to 49 other males of the same
age group who had not experienced heart attacks. Those with
prior heart attacks had significantly lower levels of DHEAS
than the control group.23
The researches concluded that serum DHEAS levels are inversely
related to premature myocardial infarction in males and that
this association is independent of the effects of several
known risk factors for premature myocardial infarction.
Another study correlating DHEAS blood levels with the level
of premature atherosclerosis in 206 patients under age 50
found that the levels of DHEAS were lower in the men who had
coronary artery disease than the control group. This data
lends further support to clinical studies suggesting that
DHEA may play an important role in the pathogenesis of coronary
A current study of 1,700 men aged 40 to 70 who had their DHEAS
levels tested indicated those with the lowest levels were
the most likely to have had heart disease, even after controlling
for other risk factors such as smoking and diet.25
Clinical studies thus far confirm that high DHEA(S) levels
are protective of heart disease in men, but not as influential
in women. It is probable, however, that supplementation with
DHEA can slow the onset of coronary artery disease.
A study was conducted of nine healthy men with an average
age of 64 years. Each was given 50 mg of DHEA for 20 weeks
at which time it was found that DHEA therapy had significantly
elevated natural killer cells that fight infections.26
Another clinical study vaccinated a group of elderly volunteers
(over 65 years of age) with the influenza vaccine and compared
them to another group similarly vaccinated but who had also
received 50 mg of DHEAS for two consecutive days beginning
on the day of the vaccination. The elderly who got the DHEAS
had a significant improvement in their ability to develop
anti-bodies to the influenza vaccine.27
In short term studies on human subjects, DHEA has been found
to be beneficial as a supplement in older individuals by improving
the immune system.
DHEA may influence women more strongly than men where sexual
desire is concerned. DHEA's favorable association with sex
drive in women was demonstrated in a Crenshaw Clinic research
protocol.28 Increased levels of DHEA were associated
with increased sexual desire.
Only in women, in marked contrast with other mammals, can
the ovaries be removed without a predictable reduction of
sexual desire. From this, researchers have concluded that
human female sexual desire has shifted somewhat from estrogens
to androgens like DHEA, and from the ovaries to the adrenals.29
In men, the positive effects of DHEA are most apparent in
those who have low androgen levels.30,31
for men, cardiovascular disease and stress are the greatest
causes of sexual dysfunction.
DHEA blood levels drop drastically under stress, which is
one of the primary reason that sex drive may decrease with
acute or chronic stress, (and why men may lose erections when
they worry about performance).32
It is clear from numerous studies that DHEA does boost sex
drive, especially in those who have low DHEAS levels.
Aging is associated with a gradual shift from a young state
characterized by anabolism, the building-up of muscles and
tissues, to an aged state characterized by catabolism, the
loss of muscle mass and strength.33
DHEA in appropriate replacement doses appears to have remedial
effects with respect to its ability to induce an anabolic
growth factor, increase muscle strength and lean body mass
in aging men and women, with no significant side effects.34
Ninety-six patients with coronary artery disease had their
DHEAS levels measured prior to starting a controlled exercise
program. After 12 weeks, there was no change in the levels
of DHEA leading researchers to conclude that exercise training
alone has no significant impact on DHEAS.35
In an earlier study conducted at the University of Rochester
in New York, eight healthy young men were given 1,600 mg of
DHEA for 4 weeks. The researchers found that DHEA had little
influence on energy or protein metabolism.36
DHEA in appropriate doses does appear to increase muscle strength
and lean body mass in older men and women. However, it has
little or no anabolic affect on younger men with normal DHEA
blood serum levels and high dosage use by bodybuilders should
In surgical menopause with the removal of the uterus and ovaries,
osteoporosis can occur within two years. After four years,
over 60% of women demonstrate osteoporosis because of estrogen
Research conducted in Japan on 120 postmenopausal women 51
to 99 years old found that women with higher DHEAS levels
were more likely to have stronger bones.38
Results of such studies demonstrate that DHEA is converted
to estrone in osteoblasts, and this is important in maintaining
bone mineral density after menopause.39
DHEA therapy has the potential to influence stronger bone
formation, especially in postmenopausal women.
The reports in the medical literature evaluating the relationship
of DHEA to weight loss have not been inconsistent.
Studies conducted in 198840 and 199141 under
Dr. Nestler at the Medical College of Virginia in Richmond
"suggest that DHEA may possess hypolipidemic and, possibly,
Similar independent studies conducted by Dr. Usiskin42
and Dr. Welle43 in 1990 concluded that short-term
administration of DHEA, in high doses, did not have much of
an influence on weight.
Recent epidemiological studies conducted this year also do
not support the theory, based upon rodent studies, that high
DHEA(S) levels protect against obesity.44
It appears unlikely that DHEA, regardless of dosage, will
facilitate weight loss, however, DHEA may potentially be combined
with other weight loss nutrients and herbs to have a synergistic
effect. More research needs to be conducted.
FACTOR FOUR FORMULATION
is manufactured from the steroidal saponin diogenin and converted
by a series of eight chemical reactions into pure dehydroepiandrosterone.
When a DHEA capsule is swallowed, it is absorbed from the
intestinal tract into the portal vein where it is transported
into the liver. Most of the DHEA is metabolized by the liver
before circulating throughout the bloodstream to the rest
of the body.1
When DHEA is metabolized, a chemical called sulfate is added
which consists of the mineral sulfur combined with oxygen,
creating DHEAS - short for DHEA-sulfate. About 90% of this
steroid hormone is in the DHEAS form with the balance circulating
as DHEA 2
It is important to note that DHEA is lipophilic (soluble in
fat) while DHEAS is water soluble. DHEA can cross the blood-brain
barrier and influence the brain whereas DHEAS cannot.3
Some manufacturers "micronize" DHEA, a process that
creates smaller particles that can be absorbed from the intestines
into the lymphatic system and partially bypass the liver,
thus increasing the amount of "free" DHEA in the
blood. Such micronization has been touted as enhancing the
bioavailability of DHEA although there is very limited data
supporting this claim.4
Titan Laboratories does not micronize its DHEA because (1)
limited data exists regarding the impact of DHEA on the brain.5
Titan is therefore reluctant to alter or "shortcut"
the natural pathway of DHEA as it is produced by the adrenals.
(2) DHEAS is consistently stable on a daily basis while free
DHEA cycles throughout the day and may increase up to a hundredfold
at a given moment or drop drastically under stress.6
Again, Titan is reluctant to alter the naturally occurring
90/10 percentage relationship of DHEAS to free DHEA pending
further clinical studies.
Drucker, MD, et al., "Biologic activity of DHEA in man",
J Clinical Endocrinol
Metab, vol 35, pp. 48-54, 1972
3. Akwa, Y, et al., Journal Cell Biology, vol 121, no. 1,
pp. 135-43, 1993
4. Casson, PR, et al., Seminars in Reproductive Endocrinology,
vol 13, no. 4,
pp. 247-54, 1995
5. Robel, P, et al., Brain Endocrinology, Raven Press, NY,
6. Glaser, J, et al., Journal of Behavioral Medicine, vol
15, pp. 327-41, 1992
of Holistic Recommendations
7. Morales, AJ, et al., J. Clinical Endocrinol Metab., vol
78, pp. 1360-67, 1994
8. Orentreich, N, et al., J Clin Endocrinol Metab, vol 59,
no. 3, pp. 551-54, 1984
9. Birkenhager-Gillesse, E, et al., An NY Acad Science, vol
719, pp. 543-52, 1994
10. dePeretti, E, et al., J Clin Endocrinol Metab, vol 47,
no. 3, pp. 572-7, 1978
11. Longscope, C, "Metab of DHEA", An NY Acad Sci,
vol 74, p. 143-48, 1995 12. Labrie, F, "Intracrinology",
Mol Cell Endocrinol, vol 78, pp. C113-18, 1991
14. Johnson, A, The Lancet, vol 347, pp. 367-9, 1996
15. Suzuki, T, et al., Clinical Exp Immunol, vol 99, no. 2,
pp. 251-5, 1995
16. van Vollenhoven, RF, et al., Arthritis Rheum, vol 37,
no. 9, pp. 1305-10, 1994
17. Morales, A, et al., "Effects of replacement dose
of DHEA in men and women
of advancing age", J Clin Endocrinol Metab, vol 78, pp.
18. Friess, E, Max Planck Inst of Psychiatry Clin Inst, Sci
Report, pp. 108-9, 1994
19. Schwartz, AG, et al., Nutr Cancer, vol 3, pp. 46-53, 1981
20. Feher, TK, et al., Journal of Steroid Biochem, vol 23,
pp. 153-7, 1985
21. Casson, P, et al., Fertil Steril, vol 63, no. 5, pp. 1027-31,
22. Bates, CW, et al., Annals NY Academy Science, pp. 291-93,
23. Mitchell, LE, Circulation, vol 89, pp. 91-93, 1994
24. Herrington, D, Annals NY Academy Science, vol 774, pp.
25. Feldman, H, Medical Tribune, p. 1, Apr. 4, 1996
26. Yen, SS, et al., Annals NY Academy Science, vol 774, pp.
27. Araneo, B, Annals NY Academy Science, vol 774, pp. 232-48,
28. Crenshaw, TL, et al., J of Sex Martial Therapy, vol 13,
pp. 239-52, 1987
29. Cumming, DC, et al., J Clin Endocrinol Metab, vol 54,
pp. 1069-71, 1982
30. de Peretti, E, et al., J Clin Endocrinol Metab, vol 47,
No. 3, pp. 572-7, 1978
31. Belanger, A, et al., J Clin Endocrinol Metab, vol 79,
pp. 1086-90, 1994
32. Labbate, L, et al., Psychosomatics, vol 36, no. 6, pp.
33. Sahelian, R, DHEA, A Practical Guide, Avery Pub Gp, Gar
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34. Yen, SS, et al., Annals NY Academy Science, vol 774, pp.
35. Milani, R, et al., Am Journal Medical Science, vol 310,
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36. Welle, S, et al., J Clin Endocrinol Metab, vol 71, no.
5, pp. 1259-64, 1990
37. Rozenberg, SH, et al., "Age, steroids and bone mineral
content", Maturitas, vol
12, pp. 137-43, 1990
38. Nawata, H, et al., J Steroid Biochem Mol Biol, vol 53,
pp. 165-74, 1995
39. Gaby, A, Nutrition and Healing newsletter, Sept. 1995
40. Nestler, J, et al., J Clin Endocrinol Metab, vol 66, pp.
41. Nestler, J, jet al., J Steroid Biochem Mol Biol, vol 40,
pp. 599-605, 1991
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5, pp. 1259-64, 1990
44. Barrett-Conner, E, et al., J Clin Endocrinol Metab, vol
81, no.1, pp.59-64,1996
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