Fall Skin Care Sale

Life Extension Magazine

LE Magazine March 2003

image

The Death of Anti-Aging Supplements?

The role of DHEA in cancer prevention

image

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

image

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

image

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.

image


Back to the Magazine Forum