REDUCES INFLAMMATION,
ENHANCES IMMUNITY, PROTECTS ARTERIES AND THE
BRAIN - by Ivy
Greenwell
Dehydroepiandrosterone
(DHEA) hormones are the most abundant steroids
in the human body. Low levels of DHEA are
associated with aging and disease states.
Specifically, a deficiency of DHEA has been
found to correlate with immune dysfunction,
inflammation, greater risk of certain cancers,
heart disease in men, and osteoporosis. The
special interest in DHEA replacement, however,
stems from its function as a prohormone, meaning
a precursor to a great variety of beneficial
steroids, both in the estrogenic and androgenic
family, on an “as-needed” basis.
Perhaps the most exciting
new finding relates to the antiatherogenic
benefits of DHEA. The dramatic aging-related
drop in DHEA levels is accompanied by an equally
dramatic rise in cardiovascular disease. We have
now come closer to elucidating the
cardioprotective mechanism of DHEA. It appears
that DHEA is incorporated into both high and
low-density cholesterol, protecting it from
oxidation. In the aged, however,
cholesterol-bound DHEA becomes virtually
undetectable, and the cholesterol molecules are
much more susceptible to oxidation than in young
individuals. But this is not the end of the
story. It turns out that DHEA also increases the
activity of platelet superoxide dismutase (SOD),
one of our most important antioxidant enzymes.
Thus, DHEA seems to play an essential role as
part of the body’s antioxidant defenses.
Another recent finding
involves the anti-inflammatory properties of
DHEA. It has been known for a long time that
DHEA can lower the levels of interleukin-6
(IL-6), a pro-inflammatory cytokine (meaning a
chemical messenger used by the immune system)
that seriously escalates the inflammatory
process, recruiting immune cells that often end
up destroying healthy tissue as well. Now it has
been established that DHEA can lower the
production of another inflammatory cytokine as
well, one called tumor necrosis factor alpha
(TNF-alpha). The levels of both IL-6 and
TNF-alpha rise with aging, showing an increased
inflammatory state and possible immune
dysfunction. The role of DHEA in regulating the
immune response has been shown to include also
the enhanced secretion of interferon-gamma. The
decline in DHEA levels is closely tied to
immunosenescence.
This is excellent news for
those who suffer from chronic inflammatory
diseases. However, it could be argued that aging
itself is, in a sense, a chronic inflammatory
state. The levels of various chemical mediators
of inflammation, such as IL-6 and TNF, increase
as we age. At the same time, our production of
DHEA plummets with aging. Maintaining youthful
levels of DHEA means less chronic inflammation.
It should be pointed out that chronic
inflammation is known to play a critical role in
the development of the killer diseases of aging:
heart disease, Alzheimer’s disease and certain
types of cancer.
More good news includes also
the finding that DHEA protects brain tissue
under conditions simulating stroke and trauma
damage, and is likely to be involved in
protecting the brain against the development of
Alzheimer’s disease. The neuroprotective
mechanism of DHEA appears to go beyond its anti-glucocorticoid
effect, that is, its ability to antagonize the
harmful effects of cortisol; anti-inflammatory
action is likely to be involved as well. DHEA
has also been shown to lower hyperglycemia
(elevated blood sugar) in diabetic rats, and
protect their kidneys from the damage caused by
high blood sugar. In addition, DHEA enhances the
immune response and helps us fight infection;
several studies have confirmed its usefulness in
combating bacterial, parasitic and viral
infections, including HIV. DHEA also helps
protect the thymus against cortisol-induced
atrophy.
Speaking of cortisol, we are
beginning to understand that it is the ratio of
DHEA to cortisol that is of critical importance
in aging and certain diseases such as AIDS. A
recent French study done at the Pasteur
Institute in Paris found that the minority of
patients who do not succumb to the severe side
effects of highly aggressive antiretroviral
therapy show a normalized DHEA/cortisol ratio.
The majority of AIDS patients, however, have an
abnormally low DHEA/cortisol ratio and thus
suffer from symptoms usually associated with
excess cortisol, even though their cortisol
levels are within normal. Cardiac patients and
the victims of Alzheimer’s disease also show low
DHEA/cortisol ratio. The manipulation of this
crucial ratio, including DHEA therapy, could
prove highly significant both in the treatment
of AIDS and in anti-aging medicine in general.
In fact, a small pilot study has already
indicated that DHEA combined with an
anti-inflammatory drug such as indomethacin can
moderate or even normalize the various
pathological changes of AIDS-related
lipodystrophy.
One surprising finding
showed that an 80 mg/day dose of DHEA can help
some infertile patients ovulate and become
pregnant, making previously ineffective ovarian
stimulation succeed at last (in one case, the
result was twins!). An animal study confirmed
that DHEA is important as a steroidogenic
substrate (precursor of other hormones) in
ovarian production of various sex steroids.
Interestingly, immunomodulatory 7-hydroxy
metabolites of DHEA have also been discovered in
human semen, with possible further implications
for fertility. In postmenopausal women, research
on DHEA replacement continues to indicate
improved well-being and libido, among many other
benefits. We are also closer to understanding
the mechanism through which DHEA enhances the
sense of well-being: it significantly increases
the levels of beta-endorphins.
Those readers who are
considering following a ketogenic
(low-carbohydrate) diet may be interested in a
small study done on rheumatoid arthritis
patients: the low-calorie ketogenic diet using
less than 40 g of carbohydrates per day resulted
in a 34% rise in DHEA within a week; the
ketogenic diet was as effective as sub-total
fast in raising DHEA levels. This study needs to
be replicated, however, using a larger number of
healthy subjects. In primates, calorie
restriction has indeed been found to preserve
higher DHEA levels, indicating a slower rate of
aging. In humans, fasting is known to raise DHEA
levels in both sexes. Anorexic and bulimic women
likewise show higher serum DHEA. Exercise can
also raise DHEA in some individuals, possibly
due to the inverse relationship between DHEA and
insulin. Finally, while meditation has long been
known to increase DHEA, participation in drum
circles has also been shown to increase DHEA and
DHEA/cortisol ratio, confirming the hypothesis
that stress reduction in general boosts DHEA
production, probably through a shift of adrenal
steroidogenesis from cortisol to DHEA. High
insulin, high cortisol and low DHEA constitute a
large part of the pathological endocrine profile
of aging. Restoring the correct hormonal ratios
should be one of the primary goals of any
anti-aging program.
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References on
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