 dhea
print version
DHEA - The Next Generation
By James South MA
Dehydroepiandrosterone
(DHEA), in its sulphated form (DHEA-S), is the most plentiful adrenal steroid
circulating in the human bloodstream. Along with the major human glucosticoid,
cortisol, DHEA is produced in the adrenal cortex. DHEA circulates primarily as
DHEA-S, which is generally metabolically inactive. As cells take DHEA-S from the
blood, they reconvert it into DHEA, and possibly other metabolites. The pregnenolone
metabolite, 17-hydroxypregnolone, is the common parent molecule for both DHEA
and cortisol.(2) Humans, along with some other primates, are unique in having
adrenals which secrete large amounts of DHEA/DHEA-S.(1) "Adrenal secretion
of DHEA and DHEA-S increases in children at the age of 6 - 8 yr, and maximal values
of circulating DHEA-S are reached between the ages of 20-30 yr. Thereafter, serum
DHEA and DHEA-S levels decrease progressively. In fact, at 70 yr of age, serum
DHEA-S levels have decreased to approximately 20% of their peak values, and they
further decrease to only 5% [of their peak values] by the age of 85-90 yr. It
is remarkable that up to 60% of the age-related decrease in serum DHEA and DHEA-S
concentration, however, takes place before the age of 50-60 yr." (1)
There have been literally thousands of scientific articles published on the
metabolic and health properties of DHEA during the last 50 years, yet only in
the 1990's did a reasonably clear picture of DHEA's role in human health and physiology
begin to emerge. Ironically, one of the chief perplexities facing researchers
has been the amazingly wide diversity of DHEA's effects. DHEA has been reported
to have anti-diabetic, anti-dementia, anti-obesity, anti-carcinogenic, anti-stress,
immune-enhancing, anti-viral and anti-bacterial, anti-aging and anti-heart disease
effects. (3,4,5). One paper alone lists eight different possible mechanisms of
DHEA's "protean physiologic activity," aside from any possible standard
steroid-genetic effects. (5) In order to better understand the wide-ranging protective
power of DHEA, it will be helpful to survey some recent studies which highlight
DHEA's role as "molecular Superman."
IMMUNE EFFECTS
It is in the field of immunology that DHEA has perhaps shown its most broad-spectrum
positive action. A recent study found a strong inverse correlation between human
serum DHEA-S levels and interleukin 6 (IL-6) levels. IL-6 is one of many cytokines,
or immune cell "quasi-hormones," which collectively regulate immune
activity. High IL-6 levels are implicated as a causal factor in many diseases,
such as rheumatoid arthritis, osteoporosis, B-cell cancers, atherosclerosis and
Parkinson's disease. (7) IL-6 levels tend to dramatically increase with aging,
just as DHEA-S levels decrease with aging. (6) After studying 120 healthy human
subjects, 15-75 years of age, R.H. Straub and colleagues concluded: "decreased
DHEA serum concentrations during aging or inflammatory diseases will be paralleled
by a significant increase in IL-6 production. Thus, we conclude that the decrease
in DHEA levels is a deleterious process, in particular during chronic inflammatory
diseases."(7)
In a recent study with eleven postmenopausal women,
P.R. Casson and co-workers administered 50 mg DHEA daily in a double-blind crossover
study. They reported that "The major finding in this study was the dramatic
enhancement in natural killer cell activityÉ. This natural killer cell
enhancement was seen in each of the 11 subjects. In this study DHEA appeared to
suppress the unexplained increase in stimulated IL-6 production seen in the placebo
group" (8) Natural killer cells are a key part of the immune stystem. They
are (ideally) in constant surveillance mode, looking especially for viruses and
cancer cells to destroy.
R.A. Daynes and B.A. Araneo have published many
articles on DHEA and immunity. In a 1992 brief review paper on natural immuno-regulation,
they state: "Our studies support the concept that DHEA may function as important
regulators of the mammalian immune system in vivo. The effects of DHEA on T cells
are to enhance their ability to produce [immune-activating] IL-2, IL-3, and ¡-IFN
[gamma interferon]. Such effects only occur if the cells are activated while under
the influence of this hormone, and appear to be most prominent in lymphoid [immune]
organs that contain the greatest ability to convert the circulating precursor
DHEA sulfate to the active metabolite [DHEA] É. Replacement therapy [i.e.
giving DHEA] should therefore restore normal immuno-competence [that tends to
be lost with aging]." (9)
O.Khorram, L.Vu and S.S.C. Yen, long-time
DHEA researchers, published an important DHEA study in 1997. Nine healthy "age-advanced
men" (mean age: 63) were given 50 mg DHEA daily for 20 weeks after 2 weeks'
placebo treatment. They noted that "Our study demonstrates the stimulatory
effects of DHEA on the immune function of age-advanced men. DHEA rejuvenated the
immune system by increasing the secretion of IL-2, a potent T-cell growth factor,
increasing the number of cells expressing the [IL-2 receptor]É, and enhancing
T cell responsiveness to mitogen stimulation. All of which decline during physiologic
aging. The significant increase in NK [natural killer] cell cytotoxicity in DHEA
treated subjects was potentially related to the increased number of NK cells,
both events being mediated by [DHEA-induced] IL-2 stimulation. There were no adverse
effects noted with DHEA administration." (10)
H. Danenberg and colleagues
reported the ability of DHEA to protect mice from endotoxin (LPS) shock. LPS-endotoxins
are released from bacterial cell walls during gram-negative infections, and can
cause a high incidence of death from "endotoxic shock." They reported
that "Mortality of CD-1 mice exposed to a lethal dose of [LPS-endotoxin]
was reduced from 95% to 24% by treatment with a single dose of DHEA, given 5 minutes
before LPS." (11)
The preceding represents just the "tip of
the iceberg" of a myriad of pro-immune DHEA studies done with humans and
animals in recent years, but it should make the point: DHEA has great potential
to restore age-degraded immune systems.
DHEA vs. INSULIN
In his recent book The Anti-Aging Zone, (12) B. Sears declared age-related increases
in insulin levels/insulin resistance to be the chief "pillar of aging."
Similarly, Dilman and Dean in their masterpiece The Neuroendocrine Theory of Aging
and Degenerative Disease also consider age-related derangements of insulin /glucose
metabolism to be a chief culprit of aging and degenerative disease. (13) A growing
body of evidence indicates DHEA has a significant role to play in reducing age-related
increases in insulin levels, insulin resistance, and blood glucose. In 1995 Jakubowicz,
Beer and Rengifo reported their results from a 30 day double blind, placebo controlled
study with 22 men (mean age:57), using 100 mg DHEA nightly. Serum insulin decreased
from 35.3 to 25.8 mU/ml, while serum glucose declined from 93.4 to 88.9 mg/ml.
Serum insulin and glucose did not change significantly in the placebo group. (14)
The P. Diamond group of Quebec, Canada performed a 12 month study with 15
60-70 year old women, using a 10% DHEA cream applied to the skin. "É
a 3.8% increase (P< 0.05) in femoral fat and a 3.5% increase (P < 0.05)
in femoral muscular areas were observed at 12 months. These changes in body fat
and muscular mass were associated with a 11% decrease (P < 0.05) in fasting
plasma glucose and a 17% decrease (P < 0.05) in fasting insulin levels."
(15)
In a 1993 case report study of a 15 year old woman with Type II
diabetes, C. Buffington and co-workers reported that a 150 mg twice daily dose
of DHEA led to "É a marked improvement in insulin sensitivity, as
determined by a more than 30 % reduction in fasting and oral glucose tolerance
test insulin levels, a threefold stimulation of the rate of glucose disappearance
with intravenous insulin, and a 30% increase in insulin binding. DHEA improved
insulin sensitivity and É ameliorated the diabetic state." (16)
G.W. Bates et al gave 15 postmenopausal women (mean age:62) 50 mg DHEA for
3 weeks. They concluded that DHEA supplementation in postmenopausal women may
decrease age-related increases in insulin resistance. (17)
P. Casson and colleagues
gave 50 mg DHEA to 11 postmenopausal women in a 3-week placebo/crossover double-blind
study. They noted, "T-lymphocyte insulin binding and degradation increased
with DHEAÉ. Enhancement in T-lymphocyte insulin binding and degradation
[is] a previously defined marker of insulin sensitivityÉ." (18)
It should be obvious by now that supplementation of DHEA from early middle age
on holds the prospect of decreased insulin levels/ resistance and decreased blood
glucose - a key factor to promote healthy aging.
ENERGY AND WELL-BEING
A.J. Morales, S.S.C. Yen and co-workers published in 1994 the results of a 6 month
placebo /double-blind crossover trial of 50 mg DHEA daily in 13 men and 17 women,
age 40 - 70. One of their key findings was "É a remarkable increase
in perceived physical and psychological well-being for both men (67%) and women
(84%) É after 12 weeks of DHEA administration, whereas less than 10% reported
any change after placebo É. Specific statements of well-being ranged from
improved quality of sleep, more relaxed, increased energy, to better ability to
handle stress. Of note, there were five subjects who self-reported marked improvements
of pre-existing joint pains and mobility during DHEA replacement." (19)
F. Labrie, P. Diamond et al published a further data in 1997 from the 12
month DHEA-skin cream study previously mentioned. While focusing on the anti-osteoporosis,
bone-building benefits of DHEA, they also noted: "Well-being and an increase
in energy were reported in 80% of all women. Our data also confirm the beneficial
effects of DHEA on well-being and energy previously reported [in the 1994 Morales/Yen
study]." (1)
In 1996 a group led by C. Berr and E.E. Baulieu (the
pioneer of DHEA research) published their epidemiological results from a 4 year
study of 622 subjects over 65 years of age living in a small community in France.
Among the 356 women assessed, lack of limitation in activities of daily living,
lack of confinement to bed or home, lack of dyspnea [shortness of breath], lack
of depressive symptoms, self-perceived good health, general life satisfaction
and low medication use were all statistically significantly correlated with high
mean levels of DHEA-S. Among men (266) only self-perceived good health and low
medication use were statistically correlated with high mean DHEA-S levels. Clearly,
for the elderly women of this study, high (natural) levels of DHEA-S were strongly
correlated with well-being and quality of life. (20)
In a 1999 study,
M. Bloch et al used a double blind crossover trial of DHEA to treat 15 patients
suffering from midlife dysthymia (minor depression of middle-age onset). There
was a 60% improvement during the DHEA phase, while only 20% improvement during
the placebo phase. "The symptoms that improved most were anhedonia [lack
of joy in daily living] loss of energy, lack of motivation, emotional 'numbness',
sadness, inability to cope, and worry". (2)
The authors note that
due to lack of correlation between baseline DHEA-S levels and positive therapeutic
response "one cannot infer that the mood disorder in any way reflects a defiency
of DHEA." (21) Nonetheless, the study clearly showed the ability of DHEA
to significantly enhance energy and well-being in people where that was seriously
lacking.
DEMENTIA
Two of the most feared and debilitating
impairments of old age are Alzheimer's dementia (AD), and multi-infarct dementia
(MID), which is the result of numerous mini-strokes. A growing body of DHEA literature
connects low DHEA levels with both AD and MID.
D.Rudman, K. Shetty and
D. Mattson published a major study on DHEA and the elderly in 1990. They compared
DHEA-S levels in 50 independently-living community men, age 55 - 94 with DHEA-S
levels in 61 nursing home men, age 57 - 104. "DHEA was significantly lower
in the nursing home men [who were generally more debilitated] than in the community
men. Plasma DHEA-S was subnormal (less than 30 mcg/dL) in 40% [25] of the nursing
home residents and in only 6% [3] of the community subjects É. In the nursing
home men É plasma DHEA-S was inversely related to the presence of an organic
brain syndrome [AD or MID] and to the degree of dependence in activities of daily
living. Plasma DHEA-S was subnormal in 80% of the nursing home men who required
total care. In total care patients with either [AD] or [MID] the prevalence of
low DHEA-S was 68% and 100% respectively." (3)
B. N…sman and
co-workers compared 45 AD and 41 MID patients to an elderly control group. They
state: "Patients with AD and MID had significantly lower serum DHEA-S values
than the control groupÉ. the ratio of plasma cortisol to serum DHEA-S was
higher in AD and MID patients than in healthy controls. DHEA has been suggested
to act as an antiglucocortiticoid. A high cortisol/DHEA-S ratio in demented patients
may thus damage hippocampal cells [these mid-brain "memory cells" die
off in organic dementia] especially - as these neurons are preferentially sensitive
to the toxic effects of [cortico]steroids." (22)
T. Yanase and colleagues
also found low DHEA-S levels in AD and CVD (cerebrovascular dementia). "We
also determined the serum concentrations of DHEA-S in 19 patients with AD, 21
patients with CVD and 45 age and gender matched elderly control individuals É.
The patients with AD and the patients with CVD were found to have lower concentrations
of serum DHEA-SÉ. Interestingly, one preliminary clinical trial based on
an intravenous administration of 200 mg a day of DHEA-S for 8 weeks suggested
slight and modest improvements in cognition and behavior in patients with AD and
CVD, respectively." (2)
H.D Danenberg et al reported findings in
1996 that may help explain a key aspect of DHEA's anti-dementia neuroprotection.
"Amyloid b protein (Ab) is the major component of senile plagues, a distinct
lesion in brain tissue of AD patients." These toxic amyloid deposits which
gradually kill AD brain cells are produced from amyloid precursor protein (APP)
by a specific enzymatic pathway - the "amyloidogenic pathway." "DHEA
treatment increases APP processing via the nonamyloidogenic pathway and may reserve
the [gradual accumulation of toxic Ab proteins] observed in the elderly. The increase
in APP production in DHEA-treated cells is accompanied by increased secretion
of the nonamyloidogenic [non-toxic protein forms]. These [non-toxic] isoforms
demonstrate neuroprotective properties, and participate in neurite outgrowth.
Thus, not only is increased production of APP not ultimately [harmful], it may
be beneficial when followed by [nonamyloidogenic processing]. It is possible that
the age-associated decline in DHEA levels may contribute to the pathological APP
processing and eventually to the development of AD." (24)
Thus,
there is hope for protecting the structure and function of aging brains through
long-term DHEA supplementation.
IGF-1
One of the most exciting
results of 1990's DHEA research has been the discovery that it may enhance insulin-like
growth factor -1 (IGF-1) release. IGF-1 (formerly called "Somatomedin C")
is the "hidden anabolic power behind the throne" of growth hormone (GH).
GH stimulates the liver to produce and release IGF-1. It is the IGF-1 that then
circulates through the bloodstream and leads to the anabolic (tissue-building)
actions GH gets credit for. (19)
The Morales/Yen study previously referred
to under ENERGY & WELL-BEING also found significant increases in both men
and women in IGF-1 status. "DHEA replacement induced an approximately 10%
rise in serum IGF-1 levels and an approximately 19% decline in IGFBP-1 [IGF-1
binding protein] levels, resulting in an IGF-1/IGFBP-1 ratio by 50% in both men
and women." (19) The authors also remark that the increased IGF-1/IGFBP-1
ratios suggest "an increased bioavailability of IGF-1 to target tissues."
(19)
Yen, Morales and Khorram conducted a one year double-blind placebo-controlled
crossover experiment with 100 mg DHEA with 16 men and women, age 50-65 years.
A significant increase in IGF-1 levels occurred in both men and women after 6
months' DHEA treatment, while IGF-1 levels dropped below baseline levels during
placebo. Men gained approximately 20% in IGF-1, while women gained about 30% in
serum IGF-1. The relative increase in IGF-1 was greater in those with low DHEA-S
levels at baseline. (31)
The Jakubowicz study previously mentioned under
INSULIN also found a significant increase in IGF-1 from 100 mg DHEA nightly for
30 days. "Serum IGF-1 increased from 96.7É to 183Éng/ml (p<0.001)É.
Serum concentration of É IGF-1 did not change in the placebo group."
(14)
In the Khorram study previously mentioned under IMMUNE ASPECTS,
50 mg DHEA daily for 20 weeks also led to increased IGF-1. Khorram et al note
that "DHEA administration resulted in a 20% increase (p < 0.01) in serum
IGF-1m a decreasing trend in IGFBP-1, and a 32% increase in the ratio of IGF-1
/IGFBP-1 (p< 0.01)." (10) The authors also report a 4-fold increase in
the DHEA-S/cortisol ratio. (10) As will become evident shortly, this major increase
in DHEA-S/cortisol ratio may hold the key to many of DHEA's diverse benefits.
In 1995 E. Bernton and colleagues reported their results from testing U.S.
Army Ranger School trainees during their gruelling training, which included a
loss of 8-15% of bodyweight over 8 weeks from intentional caloric deprivation
and continuous physical work, limitation of sleep to 4 hours per night, and long
exposures to extreme environments.
They reported a decrease in mean salivary
DHEA/cortisol ratio from 0.076 to 0.041 (p< 0.001), and a mean decrease of
serum IGF-1 of 60% during Ranger training, while GH increased 4-fold, "reflecting
a dissociation of growth hormone from IGF-1 secretion, attributable in part to
negative [food] energy balance and high cortisol levels É. In vivo, IGF-1
levels are therefore increased by glucocorticoids [i.e. cortisol] and increased
by É DHEA É. We hypothesize that tissue ratios of DHEA to cortisol
may regulate IGF-1 secretion in stressed individuals such as ranger trainees."
(25)
DHEA: NATURAL COUNTER-REGULTOR OF CORTISOL
The emphasis on the DHEA/cortisol ratio as a key health determinant is hardly
unique to the Army Ranger and Khorram studies just described. Most of the papers
I reviewed to prepare this article specifically mention DHEA's anti-glucocorticoid
(i.e. anti-cortisol) action and/or the DHEA/cortisol ratio as key factors in DHEA's
benefits. The following assessment by Regelson and Kalimi, veteran DHEA researchers,
is somewhat typical of the DHEA literature: "Among the myriad of biological
actions, the anti-glucocorticoid properties of DHEA are now clearly emerging.
In fact the anti-glucocorticoid action of DHEA may explain many of the seemingly
diverse biological activities of DHEA, such as its effects on stress, obesity,
diabetes, immune response and protection against acute lethal viral infections."
In fact, even Regelson and Kalimi's enumeration of areas of biological effect
of the antagonistic action of DHEA and cortisol does not go far enough. I listed
14 of the key properties of cortisol (excess) action - i.e. its "dark side."
[Refer to Table 1.] As can be seen from Table 1, DHEA has actions opposite to
cortisol in all 14 areas listed. It thus becomes obvious that one of the key functions
of DHEA is to serve as a counter-regulator to cortisol - to "put the brakes
on the cortisol gas pedal," as it were - so that cortisol's catabolic (tissue-destroying)
actions do not get out of control. And since cortisol tends to remain constant
or increase with age (cortisol also increases dramatically with severe/prolonged
stress), while DHEA drops dramatically with age/stress, it is obvious that there
is a general life-long, progressively worsening failure of DHEA to oppose the
catabolic excesses of cortisol.
B. Sears calls excess cortisol the "second
pillar of aging", (12) while Dilman and Dean also focus on the general age-related
failure of human physiology to control cortisol levels. (13)
Thus, it
should be clear that maintaining a lifelong high DHEA /low cortisol ratio is a
key anti-aging strategy. And the simplest way to maintain high blood levels of
DHEA from the 30's onwards is through DHEA supplementation.
DHEA
SUPPLEMENTION: POSSIBLE CONCERNS
The biggest concern over DHEA supplementation
repeatedly raised in the DHEA scientific literature is the issue of androgen/estrogen
production from DHEA. Various tissues can locally convert DHEA to either androgens
(testosterone, dihydrotestosterone, androstenedione) or estrogens (estrone, estradiol).
Many DHEA studies report significant androgen increases in women, even at the
relatively low dose of 50 mg. (1, 8, 18, 19, 21) Increased androgen levels in
women may relate not only to the mild effects of excess facial hair and acne,
but to the more serious issues of abdominal obesity, hyper-glycemia and insulin
resistance. (26) And one report found a decreased testosterone level in men, combined
with an increase in estradiol, hardly ideal for a man's health. (21) Fortunately,
a natural metabolite of DHEA, normally found in the human body, and which cannot
be bio-transformed into androgens or estrogens, (28) is now available. And preliminary
evidence indicates this "new" DHEA metabolite may be even more potent
than DHEA.
7-KETO - DHEA TO THE RESCUE!
7
- keto - DHEA (7KD) (also called "7 -oxo-DHEA,)" is almost identical
in structure to DHEA (see Diagram 1). Human skin (and other tissues) contain enzymes
that convert DHEA to 7KD in a two-stage process. (27) (Interestingly, many animal
experiments with DHEA get best results if the DHEA is given subcutaneously, hinting
at skin DHEA bio-processing.) Research into 7KD has been conducted primarily by
Dr. Henry Lardy and associates at the University of Wisconsin. (28, 29, 30) Based
on his research, Lardy has been granted various patents on the use of 7KD, including
immune enhancement/modulation, Alzheimer's treatment and weight loss.
"7-keto-DHEA has been evaluated in both preclinical studies and human clinical
trials for safety. These studies show no mutagenic activity and no adverse effects
for 7-keto-DHEA up to doses of 2000 mg /kg in rats and 500 mg /kg in primates.
It should be noted that 500 mg /kg is É 3.5 grams in a normal 70 kg human."
(30) Zenk notes that a clinical trial conducted to measure the effects of 7KD
on several endocrine and safety parameters in healthy adult men found 7KD to be
safe and well-tolerated at doses up to 200 mg/day of a 28-day period. (30) Zenk
also reports that laboratory safety tests also showed 7KD does not affect haematology,
serum chemistry, or urine chemistry differently than healthy subjects taking placebo.
(30)
Lardy has found that 7KD (7-oxo-DHEA) is a potent increaser of liver
thermogenic enzymes. He reports that "The 7-oxo-derivatives of both DHEA
[i.e. 7KD] and androstenediol are the most active compounds tested. over the range
of 0.01 to 0.1% of the diet, 7-oxo-DHEA was 2.5 times as active as DHEA."
(28) Research at the University of Wisconsin found 7KD helpful in treating primates
infected with Simian Immunodeficiency Virus (SIV). CD-4 (T helper) cell counts,
CD-8 cell counts, and total white blood cells increased. The SIV-infected primates
also showed improvements in their physical state, increased weight, and overall
improvement in behavior and clinical condition. (30)
7KD was also shown
to increase IL-2 production better than DHEA, in human lymphocytes. IL-2 is the
key cytokine regulator of T-helper cells, along with interferon-gamma, which activates
the immune system to "go into battle" against invading pathogens. (30)
Lardy and colleagues also found 7KD to enhance memory in 2-year old mice. "The
mice were trained to negotiate a water maze and then were given DHEA or 7-keto
DHEA É. They were retested after two weeks. The control mice took 34 seconds
[to negotiate the maze]; those on DHEA took 22 seconds; and those on 7-keto-DHEA
took only 7.6 seconds.
Dr. Lardy found similar results in mice using
scopolamine to abolish memory. When protected with 7-keto DHEA [and given anti-memory
scopolamine] the mice were able to negotiate the water maze in 6.5 seconds, compared
to 11.5 with DHEA treatment and 22 seconds with scopolamine treatment only."
(30)
7-KETO DHEA: A PERSONAL COMMENT
I have
been interested in DHEA since 1984. However, my personal experience with DHEA
was disappointing. I found DHEA to induce a severe depression after only 1 - 3
doses. I retried DHEA about a dozen times between 1984 to 1996, always getting
the same rapid-onset depression. I talked to a doctor colleague, who reported
that she had the same response to DHEA, and that some 5-10% of her patients who
tried DHEA also experienced a relatively rapid onset of depression (1 - 10 days).
I began taking 7KD in the fall of 1998, hoping for a different response. Much
to my surprise, I found 7KD experientially very different from DHEA. I have been
taking 7KD for about 18 months now, gradually reducing my dose from 25 mg/day
to 10-15 mg/day. I have found 7KD to be an energy enhancer, anti-cortisol stress
reducer, and general revitalizing agent. I have gradually dropped 20 pounds of
weight, have experienced a significant thinning of my face away from the classic
cortisol "moon face" I was developing in recent years. I consider 7KD
one of my core anti-aging supplements. I have also used 7KD to quickly revive
2 cats traumatized from combined surgical/anaesthesia/vaccine stress. My wife
finds 7KD to be the single most energizing supplement she's ever taken.
DHEA/
7-KETO DHEA: DOSAGES
For those wishing to get the potential androgenic benefits
of DHEA, extremely low doses are advised. 10-25 mg /day for women, 20-40 mg/day
for men. Anyone suffering any serious disease or hormonal condition should only
use DHEA under competent medical supervision. 7KD may be effective at doses as
low as 5-10 mg/day, with 25-50 mg/day being probably adequate for all but medical
use in disease treatment under medical supervision.
REFERENCES
1) Labrie, F. et al (1997) "Effect of 12 month dehyroepiandrosterone
replacement therapy on bone, vagina, and endometrium in postmenopausal women"
J Clin Endrocrinol Metab 82: 3498-3505. 2) Murphy, B. & Wolkowitz, O. (1993)
"The pathophysiologic significance of hyperadrenocorticism: antiglucocorticoid
strategies" Psychiatr Ann 23: 682-90. 3) Rudman, D. et al (1990) "Plasma
dehydroepiandrosterone sulfate in nursing home men" J Ann Geriatr Soc 38:
421-27. 4) Kalimi, M. et al (1994) "Anti-glucocorticoid effects of dehydroepiandrosterone
(DHEA)" Molec Cell Biochem 131: 99-104. 5) Regelson, W. & Kalimi, M.
(1994) "Dehydroepiandrosterone (DHEA) - the multifunctional steroid"
Ann NY Acad Sci 719: 564-75. 6) Zhang, Z. & Watson, R. "DHEA in Immune
modulation and aging", in Health Promotion and Aging, R. Watson, ed. Harwood
Acad. Pub. 1999, pp. 113-23. 7) Straub, R. et al (1998) "Serum DHEA and DHEA
sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits
IL-6 secretion from mononuclear cells in man in vitroÉ." J Clin Endocrino.
Metab 83: 2012-17. 8) Casson, P. et al (1993) "Oral dehydroepiandrosterone
in physiologic doses modulates immune function in postmenopausal women" Am
J Obstet Gynecol 169: 1536-39. 9) Daynes, R. K. Araneo, B. (1992) "Natural
regulators of T-cell lymphokine production in vivo" J Immunother 12: 174-79.
10) Khorram, O. et al (1997) "Activation of immune function by dehydroepiandrosterone
(DHEA) in age-advanced men" J. Gerontol 52A: M1-M7 11) Danenberg, H. et al
(1992) "Dehyroepiandrosterone protects mice from endotoxin toxicity and reduces
tumor necrosis factor production" Antimicrob Agents Chemother 36: 2275-79.
12) Sears, B. The Anti-Aging Zone. NY: Regan Brooks. 1999. 13) Dilman, V. &
Dean, W. The Neuroendocrine Theory of Aging and Degenerative Disease. Pensacola:
Center for Bio-Gerontology. 1992. 14) Jakubowicz, D. et al (1995) "Effect
of dehydroepiandrosterone on cyclic-guanosine monophosphate in age-advanced men"
Ann NY Acad Sci 774: 312-15. 15) Diamond, P. et al (1996) "Metabolic effects
of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal
women" J Endocrinol 150: S43-S5* 16) Buffington, C. et al (1993) "Case
report: amelioratio of insulin resistance in diabetes with dehydroepiandrosterone"
Ann J Med Sci 306: 320-24. 17) Bates, G. et al (1995) "DHEA attenuates study
induced declines in insulin sensitivity in postmenopausal women" Ann NY Acad
Sci 774: 291-3. 18) Casson, P. et al (1995) "Replacement of dehydroepiandrosterone
enhances T-lymphocyte insulin binding in postmenopausal women" Fertil Steril
63: 1027-31. 19) Morales, A. et al (1994) "Effects of replacement dose of
dehydroepiandrosterone in men and women of advancing age" J Clin Endocrinol
Metab 78: 1360-67. 20) Berr, C. et al (1996) "Relationships of dehydroepiandrosterone
sulfate in the elderly with functional, psychological, and mental status, and
short-term mortality: a French community-based study" Proc Natl Acad Sci
USA 93: 13410-15. 21) Bloch, M. et al (1999) "Dehydroepiandrosterone treatment
of midlife dysthymia" Biol Psychiatry 45: 1533-41. 22) N…sman, B. et
al (1991) "Serum dehydroandrosterone sulfate in Aszheimer's disease and multi-infarct
dementia" Biol Psychiatry 30: 684-90. 23) Yanase, T. & Nawata, H. "DHEA
and Alzheimer's disease" in Health Promotion and Aging, R. Watson, ed. Harwood
Acad. Pub. 1999, pp. 63-70. 24) Danenberg, H. et al (19960 "Dehydroepiandrosterone
(DHEA) increases production and release of Alzheimer's amyloid precursor protein"
Life Sci 50: 1651-57. 25) Bernton, E. et al (1995) "Adaptation to chronic
stress in military trainees" Ann NY Acad Sci 774: 217-31. 26) Ebeling, E.
& Koivisto, V, (1994) "Physiological importance of dehydroepiandrosterone"
Lancet 343: 1479-81. 27) Faredin, I. et al (1969) "Transformation in vitro
of [4-14C] - dehydroepiandrosterone into 7-oxygenated derivatives by normal human
male and female skin tissue" J Invest Dermatol 52: 357-61. 28) Lardy, H.
et al (1998) "Ergosteroids 3 II: Biologically active metabolites and synthetic
derivatives of dehydroepiandrosterone" steroids 63: 158-65. 29) Lardy, H.
"Dehydroepiandrosterone and ergosteroids affect energy expenditure",
in Health Promotion and Aging, R. Watson, ed. Harwood Acad. Pub. 1999. pp. 33-42.
30) Zenk, J. Living Longer in the Boomer Age. NY: Advanced Research Press, 1998.
31) Yen, S.S.C. et al (1995) "Replacement of DHEA in aging men and women"
Ann NY Acad Sci 774: 128-42. 32) Griffin, J. & Ojeda, S. ed. Textbook of Endocrine
Physiology. NY: Oxford Univ. Press, 1996. pp.290-302. 33) May, M. et al (1990)
"Protection from glucocorticoid induced thymic involution by dehydroepiandrosterone"
Life Sci 46: 1627-31. 34) Brook, C. & Marshall, N. Essential Endocrinology.
Oxford: Blackwell Science, 1996. pp.66-70. 35) Nawata, H. et al (1995) "Aromatase
in bone cell: association with osteoporosis in postmenopausal women" J Steroid
Biochem Mol Biol 53: 165-74. 36) Miklos, S. et al (1995) "Dehydroepiandrosterone
in the diagnosis of osteoporosis" Acta Biomedical Ateno Parmense 66: 139-46.
37) Nester, J. et al (1988) "Dehydroepiandrosterone reduces serum low density
lipoprotein levels and body fat but does not alter insulin sensitivity in normal
men" J Clin Endocrinol Metab 66: 57-61. 38) Wolkowitz, O. et al (1997) "Dehydroepiendrosterone
(DHEA) treatment of depression" Biol Psychiatry 41: 311-18. 39) Suitters,
A. et al (1997) "Immune enhancing effects of dehydroepiandrosterone and dehydroepiandrosterone
sulphate and the role of steroid sulphatase" Immunol 91: 314-21.
DISCLAIMER: ALL INFORMATION IS EDUCATIONAL AND PROVIDED UNDER IAS TERMS AND
CONDITIONS. IT DOES NOT, AND SHOULD NOT, REPLACE THE ADVICE OF YOUR PHYSICIAN.
Last Updated: Wednesday, March 21, 2001
© 2002
International Antiaging Systems
DHEA
Home
DHEA
Ingredients Purchase
DHEA  print
version FULL
SUMMARY ABOUT SELECT DHEA (PDF Format)
 |
Please
note that it is required that you have Acrobat Reader installed on your system
to view the above documents.
You can download the latest version by clicking
here. |
|
