|
LE Magazine March 2003
The Death of
Anti-Aging Supplements?
The role of DHEA in cancer prevention
DHEA is recognized as one of the major adrenal androgens,
and many of its abilities have been well-documented. We have
learned through years of research that it enhances the immune
system, fights osteoporosis, lowers hyperglycemia (high blood
sugar) and may even help to mount a defense against HIV. But
despite all that has been learned, its complete role in the
human endocrine system continues to remain unclear. One of the
prime areas yet to be fully examined is its effect on
carcinogenesis.
To understand its role in cancer prevention and treatment,
scientists in Japan performed a study to determine whether
DHEA has a chemopreventative effect on the precursors of colon
cancer. In the study, aberrant cryptic foci (ACF) were induced
via azoxymethane into mice, which were then treated with DHEA.
ACF is a precancerous condition. The results showed that mice
treated with 0.4% and 0.8% DHEA had a significant decrease in
the number of ACF, although there were no significant
differences between DHEA-treated and control mice in terms of
the ACF size, or level of dysplasia. This is the first study
of colon cancer carcinogenesis demonstrating that DHEA
treatment can decrease the number of ACF. These results
strongly suggest that DHEA is a potential chemopreventative
agent against human colon cancer.16
In another provocative cancer study, researchers at Peking
Union Medical College in China used Dimethylbenz (alpha)
anthracene (DMBA) to induce breast carcinoma in Sprague-Dawley
rats, followed by 10 weeks of oral administration of DHEA. The
results of this experiment showed significant inhibition of
tumor development and a lower incidence of mammary carcinoma
on daily doses of 25 mg/kg DHEA. In addition, the mean tumor
volume per rat was remarkably reduced by 92%. Moreover, 25
mg/kg DHEA treatment significantly increased the carcinoma
latency for about 3.5 weeks as compared with the control.
These results prove that DHEA is a potent cancer
chemoprophylaxis agent that exhibits inhibitory potential on
mutation and chemical carcinogen in vivo and in vitro.17
Cardiovascular system
When most people hear the term "heart disease" they
typically think about coronary artery disease-the narrowing of
the arteries leading to the heart. But coronary artery disease
is just one of a staggering number of conditions that fall
under the heading of heart disease. Cardiomyopathy,
cardiogenic pulmonary edema, aortic stenosis and myocarditis
are all forms of this killer-and the list goes on.18
Owing to its dubious distinction of being the leading cause
of death for men and women in the U.S., heart disease has been
the subject of innumerable scientific studies. Not
surprisingly, an impressive amount of this research has
focused on the relationship between heart disease, age and the
concurrent drop of DHEA-with results suggesting the need to
re-establish youthful levels, especially in men
Men, it seems, are particularly receptive to the
cardioprotective action of DHEA. Numerous studies that
examined the relationship between DHEA and heart disease found
that men with low serum levels of DHEA are as much as 1.6
times more likely to develop coronary artery disease than men
with normal levels.19
Other studies revealed that DHEA is a crucial antioxidant
that helps to protect blood vessels against atherosclerosis.
Several years ago, researchers in Canada found that in elderly
patients, vitamin E does not restore the resistance of LDL to
oxidation back to the levels found in youth. DHEA, on the
other hand, did increase LDL's resistance in a dose-dependent
manner. Furthermore, they found evidence that DHEA is actually
a part of both HDL and LDL cholesterol and at youthful
concentrations its presence helps to reduce the degree of
oxidation that occurs within cholesterol. The elderly, whose
circulating levels of DHEA are diminished, have no such
defense and subsequently suffer increased cholesterol
oxidation-the primary suspect in the development of heart
disease.20
DHEA's anti-oxidizing properties were later confirmed by
researchers in Poland who found that it effectively increases
the activity of the enzyme superoxide dismutase (SOD), one of
the most important natural antioxidants and a major factor for
preventing circulatory diseases.21
It is known from prior studies that serum apolipoprotein AI
(apoAI) levels correlate with the risk of developing
atherosclerosis. Researchers in Greece have now shown that
there is a direct association between endogenous adrenal C19
steroid hormones (DHEA and androstenedione [ASD]) and serum
lipoprotein levels. In that study, the serum concentrations of
DHEA-S, ASD, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C),
triglycerides, apolipoprotein AI (ApoAI) and apolipoprotein
B100 (ApoB100) were measured in a sample of 88 healthy men.
The results revealed that low DHEA-S is an independent factor
for increased levels of atherosclerosis-inducing ApoAI,
triglycerides, LDL-C, and ApoB100.22
In the recent population-based Rotterdam Study, researchers
investigated the relationship between levels of DHEA-S and
aortic atherosclerosis among 1,032 nonsmoking men and women
aged 55-years and over. Although no clear association between
the levels of DHEA-S and the presence of severe aortic
atherosclerosis was found, a protective effect against the
progression of aortic atherosclerosis was clearly observed in
subjects with the highest percentages of available DHEA-S.
This report further bolsters the proposal that increasing the
circulating levels of DHEA provides protection against
circulatory disorders.23
Chronic inflammatory disease
Chronic inflammation is yet another common ailment
associated with aging. It is known that the levels of various
chemical mediators of inflammation, such as interleukin-6
(IL-6) and tumor necrosis factor (TNF), increase with age,
while levels of anti-inflammatory steroids, such as DHEA,
decline.24 Left uncorrected, this
distorted ratio produces a host of inflammatory disorders
whose net result is discomfort, increased physical limitations
and premature death.
Years of research have shown that increased inflammation in
the elderly is directly related to declining levels of DHEA.
Several independent studies have also agreed that in cases of
chronic inflammation (such as rheumatoid arthritis) where
adrenal dysfunction resulted in low levels of DHEA, taking
DHEA supplements is necessary to help overcome the
inflammatory response.25
 |
Recently, a team of researchers from the University of
Regensburg, Germany reaffirmed these conclusions in a study
that examined the role of DHEA in reducing the damage produced
by chronic inflammation. According to that study, DHEA and
DHEA-S inhibit T-helper lymphocyte immune reactions and
effectively exert anti-inflammatory control over the immune
response. In cases of chronic inflammation where DHEA and
DHEA-S are dramatically decreased there is only a limited
ability to restrict inflammation. These new findings support
previous studies suggesting that in cases of chronic
inflammation, it is paramount to re-establish adequate levels
of DHEA.26
Another new study published in Arthritis & Rheumatism
reported on the effects of low serum levels of DHEA in
relation to other adrenal hormones in patients with early
rheumatoid arthritis (RA) and reactive arthritis (ReA). In
that study the authors found that levels of DHEA-S were
relatively low in relation to levels of IL-6 and TNF in
untreated patients with early RA and ReA when compared with
healthy subjects. The study further demonstrated that there
was a relative increase of cortisol-a potentially harmful
steroid-in relation to DHEA-S.27
Systemic lupus erythematosus (SLE), an inflammatory
autoimmune disorder that affects approximately one in every
700 women, is another promising candidate for DHEA therapy.
Researchers at the National Defense Medical Center in China
evaluated the efficacy and tolerability of DHEA at high dosage
in women with active SLE. In a multicenter, randomized
double-blind, placebo-controlled trial, 120 adult women with
active SLE received oral doses of DHEA at 200 mg/day for 24
weeks. After the therapy concluded, results showed that the
number of patients with SLE flares receiving the DHEA
supplement orally was deceased by 16% compared with the
control group. In addition, no life-threatening reactions or
serious safety issues were observed, indicating that DHEA was
well tolerated and is effective in mitigating SLE and reducing
disease activity.28
The research continues
Whether or not DHEA proves to be the panacea of aging
remains to be seen. Effective, prolonged research dealing with
this potential biochemical miracle is still in its
infancy-despite having been discovered over 70 years ago.
However, within the past year alone scientists have taken
enormous strides in unraveling the riddle of DHEA-proving not
only its extraordinary benefit as a dietary supplement, but
also its effectiveness for treating and preventing dozens of
the most common, debilitating age-related disorders.
Already, new research is well underway to further define
and explore DHEA's place in HIV treatment, cancer prevention,
neurological trauma, osteoporosis and many other diseases that
currently offer little or no hope for the afflicted.
References
1. Allolio B, et al. DHEA treatment: myth
or reality? Trends Endocrinol Metab 2002 Sep;13(7):288-94.
2. Zdrojewicz Z, et al.
Dehydroepiandrosterone (DHEA)-youth hormone? Wiad Lek
2001;54(11-12):693-704.
3. Corrigan B. DHEA and sport. Clin J
Sport Med 2002 Jul;12(4):236-41.
4. Steckelbroeck S, et al.
Characterization of the dehydroepiandrosterone (DHEA)
metabolism via oxysterol 7alpha-hydroxylase and 17-ketosteroid
reductase activity in the human brain. J Neurochem 2002
Nov;83(3):713-26.
5. Murialdo G, et al. Hippocampal
perfusion and pituitary-adrenal axis in Alzheimer's disease.
Neuropsychobiology 2000;42(2):51-7.
6. Aragno M, et al.
Dehydroepiandrosterone prevents oxidative injury induced by
transient ischemia/reperfusion in the brain of diabetic rats.
Diabetes 2000 Nov;49(11):1924-31.
7. Karishma KK, et al.
Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the
hippocampus of the rat, promotes survival of newly formed
neurons and prevents corticosterone-induced suppression. Eur J
Neurosci 2002 Aug;16(3):445-53.
8. Yorek MA, et al. Effect of treatment
of diabetic rats with dehydroepiandrosterone on vascular and
neural function. Am J Physiol Endocrinol Metab 2002
Nov;283(5):E1067-75.
9. Weill-Engerer S, et al. Neurosteroid
quantification in human brain regions: comparison between
Alzheimer's and nondemented patients. J Clin Endocrinol Metab
2002 Nov;87(11):5138-43.
10. Almeida OP, et al. Sex hormones and
their impact on dementia and depression: a clinical
perspective. Expert Opin Pharmacother 2001
Apr;2(4):527-35.
11. Huppert FA, et al.
Dehydroepiandrosterone (DHEA) supplementation for cognition
and well-being. Cochrane Database Syst Rev
2000;(2):CD000304.
12. Arlt W, et al. DHEA replacement in
women with adrenal insufficiency-pharmacokinetics,
bioconversion and clinical effects on well-being, sexuality
and cognition. Endocr Res 2000 Nov;26(4):505-11.
13. Young AH, et al. Elevation of the
cortisol-dehydroepiandrosterone ratio in drug-free depressed
patients. Am J Psychiatry 2002 Jul;159(7):1237-9.
14. Sondergaard HP, et al. Elevated blood
levels of dehydroepiandrosterone sulphate vary with symptom
load in posttraumatic stress disorder: findings from a
longitudinal study of refugees in Sweden. Psychother Psychosom
2002 Sep-Oct;71(5):298-303.
15. Migues PV, et al.
Dehydroepiandosterone and its sulphate enhance memory
retention in day-old chicks. Neuroscience
2002;109(2):243-51.
16. Osawa E, et al. Chemoprevention of
precursors to colon cancer by dehydroepiandrosterone (DHEA).
Life Sci 2002 Apr 19;70(22):2623-30.
17. Yang S, et al. Anti-mutagenicity
activity of dehydroepiandrosterone. Zhonghua Zhong Liu Za Zhi
2002 Mar;24(2):137-40.
18. Tierney L, et al. Current medical
diagnosis and treatment. 40th ed., pp. 352-447. New York, NY:
McGraw-Hill.
19. Feldman HA, et al. Low
dehydroepiandrosterone and ischemic heart disease in
middle-aged men: prospective results from the Massachusetts
Male Aging Study. Am J Epidemiol 2001 Jan 1;153(1):79-89
20. Khalil A, et al. Age-related decrease
of dehydroepiandrosterone concentrations in low density
lipoproteins and its role in the susceptibility of low density
lipoproteins to lipid peroxidation. J Lipid Res 2000
Oct;41(10):1552-61.
21. Bednarek-Tupikowska G, et al.
Influence of dehydroepiandrosterone on platelet aggregation,
superoxide dismutase activity and serum lipid peroxide
concentrations in rabbits with induced hypercholesterolemia.
Med Sci Monit 2000 Jan-Feb;6(1):40-5
22. Zofkova I, et al. Apolipoprotein E
gene determines serum testosterone and dehydroepiandrosterone
levels in postmenopausal women. Eur J Endocrinol 2002
Oct;147(4):503-6.
23. Hak AE, et al. Low levels of
endogenous androgens increase the risk of atherosclerosis in
elderly men: the Rotterdam study. J Clin Endocrinol Metab 2002
Aug;87(8):3632-9.
24. Straub RH, et al.
Dehydroepiandrosterone in relation to other adrenal hormones
during an acute inflammatory stressful disease state compared
with chronic inflammatory disease: role of interleukin-6 and
tumour necrosis factor. Eur J Endocrinol 2002
Mar;146(3):365-74.
25. Leowattana W, et al. DHEA(S): the
fountain of youth. J Med Assoc Thai 2001 Oct;84 Suppl
2:S605-12
26. Straub RH, et al. The
endotoxin-induced increase of cytokines is followed by an
increase of cortisol relative to dehydroepiandrosterone (DHEA)
in healthy male subjects. J Endocrinol 2002
Nov;175(2):467-74.
27. Straub RH, et al. Inadequately low
serum levels of steroid hormones in relation to interleukin-6
and tumor necrosis factor in untreated patients with early
rheumatoid arthritis and reactive arthritis. Arthritis Rheum
2002 Mar;46(3):654-62.
28. Chang DM, et al.
Dehydroepiandrosterone treatment of women with
mild-to-moderate systemic lupus erythematosus: a multicenter
randomized, double-blind, placebo-controlled trial. Arthritis
Rheum 2002 Nov;46(11):2924-7.
Back to
the Magazine Forum
|