The Truth About dhea supplementation

The Truth About
DHEA Supplementation

DHEA is vital to health

DHEA is secreted by the adrenal glands, and also produced in the gonads (testes and ovaries), and brain. It is sometimes called the "mother of all hormones" because it is the building block from which estrogen and testosterone are produced, and is vital to health.

Thousands of scientific articles have been published on DHEA during the last 50 years, but a clear picture of its role in human health didn't begin to emerge until the 1990's.

DHEA exhibits an amazingly wide diversity of effects

• 
  is an antioxidant
  
• 
  is a hormone regulator (it helps regulate the thyroid & pituitary glands, and enhances thymus gland function)
  
• 
  decreases cholesterol
  
• 
  stimulates the production of human growth hormone
  
• 
  boosts immunity by stimulating killer cell activity
  
• 
  increases the sensitivity of cells to insulin
  
• 
  assists in returning the body to a balanced state after a stress reaction
  
• 
  improves cognitive function, bone formation and libido
  
• 
  enhances mood by increasing the brain's serotonin levels
  

DHEA levels decrease with age

According to Michael Galitzer, M.D., co-founder of the American Health Institute in Los Angeles, California, symptoms of a DHEA deficiency include: poor memory, poor resistance to noise, anxiety, decreased libido (especially in women), decreased armpit and pubic hair, and dry skin, eyes or hair.5

Very low levels of DHEA have been linked to cardiovascular disease in men, some cancers, trauma, and stress; low levels are also associated with old age, particularly in the unwell, institutionalized elderly. Research has also shown a correlation between low DHEA levels and a declining immune system. Also, Alzheimer patients have exhibited low DHEA levels, when compared to their healthy counterparts.

Other factors that contribute to decreased DHEA levels

• 
  disease
  
• 
  sugar
  
• 
  nicotine
  
• 
  caffeine
  
• 
  alcohol
  
• 
  nutritional imbalances
  
• 
  a vegetarian diet low in cholesterol and healthy fats 6
  

DHEA supplementation

In animal studies, replacing DHEA has had startling anti-aging effects. Large doses of the hormone have restored older animals' strength and vigor.

How does DHEA work in the body?

One of DHEA's most over-looked, but vital roles may be its ability to counter-balance cortisol — when DHEA is low, cortisol levels are high and vice-versa. Cortisol, one of the few hormones that usually increases with age, induces stress. And when it circulates at high levels for long periods of time it may affect many bodily functions, including damaging insulin resistance and the endocrine system, and the hypothalamus. Maintaining healthy levels of DHEA for aging and stressed individuals may be its most important role due to its ability to lower cortisol levels.8,9

Recent studies highlight DHEA's role as "molecular superpower"

Immune protector

Comparable findings were reported in a similar study with eleven postmenopausal women.11

Anti-obesity effects

A 1995 30-day double-blind, placebo controlled study with 22 men (mean age:57), using 100 mg DHEA nightly showed that 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.12

In a three-study with 15 postmenopausal women (mean age:62), 50 mg of DHEA was also found to decrease age-related increases in insulin resistance.13

Increases energy, improves well being

Protects brain cells from Alzheimer's disease

A major study on DHEA and the elderly published in 1990 compared DHEA-S levels in 50 independently-living men, age 55 - 94 with the DHEA-S levels in 61 men, age 57 - 104, who were living in a nursing home. The results showed that DHEA was significantly lower in the men who were living in the nursing home (and who were generally more debilitated) than in the men living independently.16

How safe is DHEA?

The biggest concern over DHEA supplementation is the issue of androgen/estrogen production from DHEA. Various tissues can convert DHEA to either androgens (testosterone, dihydrotestosterone, androstenedione) or estrogens (estrone, estradiol). DHEA studies have reported significant androgen increases in women, at a 50 mg and higher dosage 18,19,20,21 and a decreased testosterone level in men, combined with an increase in estradiol 21, which can result in acne, oily skin, facial hair growth in women, and irritability, insomnia, fatigue, and breast enlargement in men

Also, DHEA is NOT recommended for people under 30 years of age, unless indicated by blood testing; or for pregnant or nursing women; or people at risk for breast, uterine or prostate cancer.

How much should you take?

Perhaps the best answer is to be cautious and use low doses of DHEA on a regular basis. For the most accurate information, ask your doctor to do before-and-after tests of blood DHEA and DHEA-sulfate levels.

Testing for DHEA blood serum levels

Saliva test

Generally, when you order a test kit, you'll receive one or two collection tubes, a pre-paid return mailer, as well as identification forms, labels and packing materials. Then, you simply expectorate saliva into the collection tube(s), filling the tube(s) to the specified line. Finally, complete the forms, mail the package and wait for the results.

Hormone test kits and related laboratory services are available trough:

ZRT Laboratory

Powerful anti-aging tool

References:

1. 
   Rudman, D. et al (1990) "Plasma dehydroepiandrosterone sulfate in nursing home men" J Ann Geriatr Soc 38: 421-27.
   
2. 
   Kalimi, M. et al (1994) "Anti-glucocorticoid effects of dehydroepiandrosterone (DHEA)" Molec Cell Biochem 131: 99-104.
   Abstract
   
3. 
   Regelson, W. & Kalimi, M. (1994) "Dehydroepiandrosterone (DHEA) - the multifunctional steroid" Ann NY Acad Sci 719: 564-75.
   
4. 
   Regelson, William, M.D., & Colman, Carol. The Superhormone Promise. New York: Simon & Schuster, 1996.
   
5. 
   Alternative Medicine, edited by Trivieri, Larry, Jr. & Anderson, John W., Celestial Arts, Berkeley, CA. 2002.
   
6. 
   Ibid.
   
7. 
   Cherniske S. The DHEA Breakthrough. New York: Ballantine Books, 1996.
   Abstract
   
8. 
   Sears, B. The Anti-Aging Zone. NY: Regan Brooks. 1999.
   Abstract
   
9. 
   Dilman, V. & Dean, W. The Neuroendocrine Theory of Aging and Degenerative Disease. Pensacola: Center for Bio-Gerontology. 1992.
   
   Abstract
   
10. 
    Khorram, O. et al (1997) "Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men" J. Gerontol 52A: M1-M7
    Abstract
    
11. 
    Casson, P. et al (1993) "Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women" Am J Obstet Gynecol 169: 1536-39.
    Abstract
    
12. 
    Jakubowicz, D. et al (1995) "Effect of dehydroepiandrosterone on cyclic-guanosine monophosphate in age-advanced men" Ann NY Acad Sci 774: 312-15.
    
13. 
    Bates, G. et al (1995) "DHEA attenuates study induced declines in insulin sensitivity in postmenopausal women" Ann NY Acad Sci 774: 291-3.
    Abstract
    
14. 
    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.
    Abstract
    
15. 
    Fowkes, The Independent, Sept. 1, 1989, pp. 6
    
16. 
    Rudman, D. et al (1990) "Plasma dehydroepiandrosterone sulfate in nursing home men" J Ann Geriatr Soc 38: 421-27.
    Abstract
    
17. 
    Alternative Medicine, edited by Trivieri, Larry, Jr. & Anderson, John W., Celestial Arts, Berkeley, CA. 2002.
    
18. 
    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.
    
19. 
    Casson, P. et al (1993) "Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women" Am J Obstet Gynecol 169: 1536-39.
    Abstract
    
20. 
    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.
    Abstract
    

Department of Obstetrics and Gynecology, University of Tennessee, Memphis 38163.

OBJECTIVE: This study tests the hypothesis that dehydroepiandrosterone or its metabolic products are immunomodulatory in postmenopausal women with relative adrenal androgen deficiency. STUDY DESIGN: A prospective, randomized, double-blind, crossover study of 11 subjects with 3-week treatment arms separated by a 2-week washout period was performed. Immunologic evaluation at the beginning and end of the treatment arms consisted of flow cytometry to delineate T-cell populations, in vitro T-cell mitogenic response and cytokine production, and natural killer cell cytotoxicity. Statistical analysis was based on a split-plot design with analysis of variance with repeated measures. RESULTS: Dehydroepiandrosterone supplementation decreased CD4+ (helper) T cells and increased CD8+/CD56+ (natural killer) cells. Although T-cell mitogenic and interleukin-6 responses were inhibited, natural killer cell cytotoxicity increased dramatically. CONCLUSIONS: These data provide the first in vivo evidence in human for an immunomodulatory effect of dehydroepiandrosterone. The salutary immune changes could account for clinical and experimental evidence of antioncogenic effects of this steroid. This study provides a strong rationale for further clinical studies on dehydroepiandrosterone supplementation in adrenal androgen-deficient states.

21. 
    Abstract
    

Department of Reproductive Medicine, University of California, San Diego School of Medicine, USA.

22. 
    RESULTS: Baseline levels of serum DHEA sulfate (DHEAS), a stable marker of circulating DHEA levels, were 2 standard deviations below young adult values and increased 3-4 fold within 2 weeks. These levels were sustained throughout the duration of DHEA administration. When compared with placebo, DHEA administration resulted in a 20% increase (p < .01) in serum IGF-I, a decreasing trend in IGFBP-I, and a 32% increase in the ratio of IGF-I/IGFBP-I (p < .01). Activation of immune function occurred within 2-20 weeks of DHEA treatment. The number of monocytes increased significantly (p < .01) after 2 (45%) and 20 (35%) weeks of
    

The Hidden Truth About Stress

Why it can kill you … and how Magnolia Extract can alleviate its effects almost immediately!

Feeling stressed lately?
Take charge of your stress

You may even be one of the 50 million caregivers in this country, 80 percent of which say they have high levels of stress. According to the National Alzheimer's Association, nearly half of this 80 percent also suffer from depression. It's no wonder that many of these caregivers ignore their own needs and end up with a life-threatening illness themselves.

Most experts agree that stress is a major factor in disorders and diseases such as anxiety, insomnia, depression, ulcers, rheumatoid arthritis, headache, hypoglycemia, asthma, herpes, hypertension and heart disease. It's no wonder, then, that new research suggests that chronic stress speeds up the aging process of cells. Lead researcher Elissa Epel, a University of California at San Francisco (UCSF) psychiatrist, and her colleagues studied 39 women ages 20 to 50 who suffered chronic stress because they had been caring for a chronically ill child. The researchers studied telomeres—caps at the ends of chromosomes that naturally get shorter and shrivel as cells age and continue to divide. The scientists concluded that chronic stress appears to speed up this process.1

Lowered self-esteem Impulsive behavior, emotional instability Fatigue Anxiety, irrational fears Trembling, nervous tics Tendency to be easily startled Tooth grinding Nervous, generally high-pitched laughter Insomnia Stuttering and other speech difficulties Sweating Lower back pain, neck pain, chest pain Frequent urination Loss of appetite, compulsive eating Migraine headaches Increased use of prescribed drugs Excessive smoking Alcohol dependency, drug addiction Nightmares

Where does stress come from?

Although it's impossible to live a stress-free life—simply because stress is a fact of life—we have good news for you! Now it’s easier than ever to neutralize stress before it takes its toll with Magnolia Extract—an ancient Chinese herb.

Every day, one million Americans are absent from work because of stress-related disorders.

Magnolia extract is the only natural and safe remedy in the world that relieves stress, anxiety and depression

Tension headache Excess or decreased weight Muscle pain, spasms Excessive nervous energy Acne, eczema Chronic diarrhea or constipation Constant fatigue Stomach or intestinal ulcers Allergies Increased cholesterol levels Increased blood pressure Tendency toward fainting or nausea Migraine headaches Increased susceptibility to infection Impotence, sexual difficulties Increased possibility of heart disease Frequent heartburn Cardiovascular disorders Shortness of breath Inability to laugh easily or openly Recurring feelings of hopelessness with life

How does it work? Magnolia extract is rich in the phytochemicals honokiol and magnolol, which have numerous health benefits. One of the most impressive benefits is their ability to alleviate stress while producing a calming effect. Dozens of animal studies have shown that they act as a non-addictive, non-sedating anxiolytic (anti-anxiety and anti-stress) agent at low doses.4,5  That means a small dose of Magnolia extract can help calm your nerves and alleviate anxiety, without making you sleepy. The beauty about these two phytochemicals is that honokiol exerts an anti-anxiety effect, and magnolol exerts an antidepressant effect.6

Honokiol relieves stress without side effects

A similar test found that honokiol significantly prolonged the time the animals spent in a maze, suggesting an anti-anxiety effect. Normally, when rodents are placed in a maze, they like to hide rather than explore because they get anxious. These rodents appeared to be more relaxed, and expressed curiosity about their environment. When the animals were given honokiol in various doses over a period of seven days, the effects remained the same: there was no change in motor activity or in the animals' performance. The animals receiving the diazepam (Valium), however, became dependent on the same dose, which hindered their performance.8

Although no studies have specifically been done to show that Magnolia extract reduces cortisol levels, it stands to reason that since so much impressive research has shown that it relieves stress, anxiety and depression, that Magnolia must also reduce cortisol—a by-product of stress.

Alcohol Results in impaired reaction & reflexes; liver toxicity, free radical production     Caffeine Nerve stimulant; can lead to addiction; contains antioxidants     Recreational Drugs Results in impaired reaction & reflexes; contributes to liver toxicity and free radical production; can lead to addiction     Meditation & Yoga Produces an overall sense of well being; balances brain waves; takes  practice and a sense of commitment     Massage Relieves stress and muscle fatigue; results are usually temporary and short lasting     Magnolia Reduces stress, anxiety and depression almost immediately; reduces cortisol levels; provides numerous health benefits, including antioxidant protection, anticancer protection, reduction of inflammation and pain

We at Smart Publications think that more research is needed on the benefits of Magnolia and, in particular, we think research should be done to look at how Magnolia affects cortisol levels.

So far, what we do know is that when compared to pharmaceutical drugs such as Valium (diazepam), honokiol appears to be just as effective in its anti-anxiety activity, but without the strong sedative effect. This makes it an amazingly safe and effective remedy to help relieve the damaging effects of stress, without the tranquilizing side effects of drugs.

Brain health benefits

• 
  modulating the activity of various neurotransmitters and related enzymes in the brain
  
• 
  increasing choline acetyltransferase activity
  
• 
  inhibiting acetylcholinesterase
  
• 
  increasing acetylcholine release9
  

A small dose of Magnolia extract can help calm your nerves and alleviate anxiety, without making you sleepy

Powerful antioxidant protection

A number of studies have shown that Magnolia extract protected mitochondria (a cell's powerhouse) from free radical damage in the liver of laboratory animals,13,14 heart,15 and brain cells.16 It was also found to be a strong candidate in the treatment of sepsis, a severe illness caused by overwhelming infection of the bloodstream by toxin-producing bacteria.17  This is especially significant because sepsis is a problem in hospitals where drug resistant organisms are prevalent.

Shows promise as an anti-cancer agent

• 
  Could potentially be an effective drug for leukemia 18,19,20
  
• 
  Inhibited proliferation of human lung squamous carcinoma 21,22 and other tumors23
  
• 
  Decreased cancer cells in human colon and liver tumors 24-27
  

According to the research, which was published in the Journal of Biological Chemistry online on June 19, 2003, and summarized in an article on Science Blog28, tumors can't continue to grow past a certain size without the oxygen and nutrients that blood vessels provide. The most dangerous tumors put out signals that tell the body to grow new blood vessels toward them. Angiogenesis inhibitors stop those signals from being received.

The investigators found that honokiol reduced the abnormal growth of endothelial cells by driving them into apoptosis—a self-destruction program activated by cells when their growth signals are disrupted. In the study, honokiol reduced tumor growth by 50% in mice that were inoculated with tumor-promoting cells, over a control group of mice.

Jack Arbiser, MD, PhD, one of the researchers, and an Assistant Professor of Dermatology at Emory School of Medicine, and faculty member in the Winship Cancer Institute, said, "Honokiol shows promise as a drug because in mice it appears not to be excreted or broken down by the liver too quickly." He added, "Honokiol is easier to synthesize than other cancer drugs, and we've been looking into the best ways to synthesize honokiol and its derivatives in large quantities." His team is currently collaborating with organic chemists at Emory and at the University of Georgia, and looking at pharmacological properties of molecules related to honokiol.

Nothing compares to Magnolia extract when it comes to lowering stress response, anxiety and depression—almost immediately!

In addition to all these benefits, studies have shown that Magnolia extract:

• 
  Enhances steroid production by the adrenal cortex 29 which would make it a good supplement for counteracting adrenal fatigue
  
• 
  Inhibits bacteria30 and pathogenic fungi31
  
• 
  Reduces inflammation and pain32
  

• 
  Protects against seizures33
  
• 
  Acts as an antidote for pesticide poisoning34
  
• 
  Plays a significant role in alleviating and controlling asthma35-38
  

How safe is Magnolia?

Why take Magnolia Extract?

How much should you take?

Experience the difference!

See this other Article of Interest From
Smart Publications Health & Wellness Update

References

1. 
   Epel, E. Proceedings of the National Academy of Sciences, Nov. 29-Dec. 4, 2004.
   
   
   
2. 
   Leverenz1, J., Wilkinson, C., Wamble1, M., Corbin, S., Grabber, JE., Raskind, M., Peskind, E. Effect of Chronic High-Dose Exogenous Cortisol on Hippocampal Neuronal Number in Aged Nonhuman Primates. The Journal of Neuroscience, March 15, 1999, 19(6):2356-2361.
   
3. 
   Lupien SJ, Fiocco A, Wan N, Maheu F, Lord C, Schramek T, Tu MT. Stress hormones and human memory function across the lifespan. Psychoneuroendocrinology. 2005 Apr;30(3):225-42. 
   Abstract
   
4. 
   Kuribara H, Kishi E, Hattori N, Okada M, Maruyama Y. The anxiolytic effect of two oriental herbal drugs in Japan attributed to honokiol from magnolia bark. J Pharm Pharmacol 2000 Nov;52(11):1425-9.
   Abstract
   
   
   
5. 
   Maruyama Y, Kuribara H, Morita M, Yuzurihara M, Weintraub ST. Identification of magnolol and honokiol as anxiolytic agents in extracts of saiboku-to, an oriental herbal medicine. J Nat Prod 1998 Jan;61(1):135-8.
   Abstract
   
   
   
6. 
   Nakazawa T, Yasuda T, Ohsawa K. Metabolites of orally administered Magnolia officinalis extract in rats and man and its antidepressant-like effects in mice. J Pharm Pharmacol. 2003 Nov; 55(11): 1583-91.
   Abstract
   
7. 
   Kuribara H, Stavinoha WB, Maruyama Y. Honokiol, a putative anxiolytic agent extracted from magnolia bark, has no diazepam-like side effects in mice. J Pharm Pharmacol 1999 Jan;51(1):97-103.
   Abstract
   
8. 
   Kuribara H, Stavinoha WB, Maruyama Y. Behavioural pharmacological characteristics of honokiol, an anxiolytic agent present in extracts of Magnolia bark, evaluated by an elevated plus-maze test in mice. J Pharm Pharmacol 1998 Jul;50(7):819-26.
   Abstract
   
   
   
9. 
   Hou YC, Chao PD, Chen SY. Honokiol and magnolol increased hippocampal acetylcholine release in freely-moving rats. Am J Chin Med  2000;28(3-4):379-84.
   Abstract
   
10. 
    Liu B, Hattori N, Zhang NY, Wu B, Yang L, Kitagawa K, Xiong ZM, Irie T, Inagaki C. Anxiolytic agent, dihydrohonokiol-B, recovers amyloid beta protein-induced neurotoxicity in cultured rat hippocampal neurons. Neurosci Lett. 2005 Aug 12-19;384(1-2):44-7. 
    Abstract
    
11. 
    Fukuyama Y, Nakade K, Minoshima Y, Yokoyama R, Zhai H, Mitsumoto Y. Neurotrophic activity of honokiol on the cultures of fetal rat cortical neurons. Bioorg Med Chem Lett 2002 Apr 22;12(8):1163-6.
    Abstract
    
12. 
    Lo YC, Teng CM, Chen CF, Chen CC, Hong CY. Magnolol and honokiol isolated from Magnolia officinalis protect rat heart mitochondria against lipid peroxidation. Biochem Pharmacol  1994 Feb 9;47(3):549-53.
    Abstract
    
13. 
    Chiu JH, Ho CT, Wei YH, Lui WY, Hong CY. In vitro and in vivo protective effect of honokiol on rat liver from peroxidative injury. Life Sci 1997;61(19):1961-71.
    Abstract
    
14. 
    Chiu JH, Wang JC, Lui WY, Wu CW, Hong CY. Effect of magnolol on in vitro mitochondrial lipid peroxidation and isolated cold-preserved warm-reperfused rat livers. J Surg Res 1999 Mar;82(1):11-6.
    Abstract
    
15. 
    Shen YC, Sung YJ, Chen CF. Magnolol inhibits Mac-1 (CD11b/CD18)-dependent neutrophil adhesion: relationship with its antioxidant effect. Eur J Pharmacol 1998 Feb 5;343(1):79-86.
    Abstract
    
16. 
    Lee MM, Hseih MT, Kuo JS, Yeh FT, Huang HM. Magnolol protects cortical neuronal cells from chemical hypoxia in rats. Neuroreport 1998 Oct 26;9(15):3451-6.
    Abstract
    
17. 
    Kong CW, Tsai K, Chin JH, Chan WL, Hong CY. Magnolol attenuates peroxidative damage and improves survival of rats with sepsis. Shock 2000 Jan;13(1):24-8.
    Abstract
    
18. 
    Zhong WB, Wang CY, Ho KJ, Lu FJ, Chang TC, Lee WS. Magnolol induces apoptosis in human leukemia cells via cytochrome c release and caspase activation. Anticancer Drugs 2003 Mar;14(3):211-7.
    Abstract
    
19. 
    Battle TE, Arbiser J, Frank DA. The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Blood. 2005 Jul 15;106(2):690-7. Epub 2005 Mar 31. 
    Abstract
    
20. 
    Fong WF, Tse AK, Poon KH, Wang C. Magnolol and honokiol enhance HL-60 human leukemia cell differentiation induced by 1,25-dihydroxyvitamin D3 and retinoic acid. Int J Biochem Cell Biol. 2005 Feb;37(2):427-41 
    Abstract
    
21. 
    Yang SE, Hsieh MT, Tsai TH, Hsu SL. Effector mechanism of magnolol-induced apoptosis in human lung squamous carcinoma CH27 cells. Br J Pharmacol 2003 Jan;138(1):193-201.
    Abstract
    
22. 
    Yang SE, Hsieh MT, Tsai TH, Hsu SL. Down-modulation of Bcl-XL, release of cytochrome c and sequential activation of caspases during honokiol-induced apoptosis in human squamous lung cancer CH27 cells. Biochem Pharmacol 2002 May 1;63(9):1641-51.
    Abstract
    
23. 
    Ikeda K, Nagase H. Magnolol has the ability to induce apoptosis in tumor cells. Biol Pharm Bull 2002 Dec;25(12):1546-9.
    Abstract
    
24. 
    Lin SY, Liu JD, Chang HC, Yeh SD, Lin CH, Lee WS.  Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis. J Cell Biochem 2002;84(3):532-44.
    Abstract
    
25. 
    Lin SY, Chang YT, Liu JD, Yu CH, Ho YS, Lee YH, Lee WS. Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells. Mol Carcinog 2001 Oct;32(2):73-83.
    Abstract
    
26. 
    Chen F, Wang T, Wu YF, Gu Y, Xu XL, Zheng S, Hu X. Honokiol: a potent chemotherapy candidate for human colorectal carcinoma. World J Gastroenterol. 2004 Dec 1;10(23):3459-63. 
    Abstract
    
27. 
    Wang T, Chen F, Chen Z, Wu YF, Xu XL, Zheng S, Hu X. Honokiol induces apoptosis through p53-independent pathway in human colorectal cell line RKO. World J Gastroenterol. 2004 Aug 1;10(15):2205-8. 
    Abstract
    
28. 
    Science Blog. "Emory scientists find anti-tumor compounds in magnolia cones." http://www.scienceblog.com/community/modules.php?name=
    News&file=article&sid=1833. July 15, 2003.
    
29. 
    Wang SM, et al., Magnolol stimulates steroidogenesis in rat adrenal cells, British Journal of Pharmacology 2000; 131(6): 1172-1178.
    Abstract
    
30. 
    Zhu YP, Chinese Materia Medica: Chemistry, Pharmacology, and Applications, 1998 Harwood Academic Publishers, Amsterdam.
    
31. 
    Bang KH, et al., Antifungal activity of magnolol and honokiol, Archives Pharmaceutical Research 2000; 23(1): 46-49.
    Abstract
    
32. 
    Wang JP, et al., Anti-inflammatory and analgesic effects of magnolol, Archives Pharmacology 1992; 346(6): 707-712.
    
33. 
    Chiou LC, Ling JY, and Chang CC, Chinese herb constituent beta-eudesmol alleviated the electroshock seizures in mice and electrographic seizures in rat hippocampal slices, Neuroscience Letters 1997; 231(30; 171-174.
    Abstract
    
34. 
    Chiou LC, Ling JY, and Chang CC, beta-Eudesmol as an antidote for intoxication from organophophorus anticholinesterase agents, European Journal of Pharmacology 1995; 292(2): 151-156.
    Abstract
    
35. 
    Homma M, Oka K, Kobayashi H, Niitsuma T, Yamamoto S, Itoh H, Takahashi N. Impact of free magnolol excretions in asthmatic patients who responded well to saiboku-to, a Chinese herbal medicine. J Pharm Pharmacol 1993 Sep;45(9):844-6.
    Abstract
    
36. 
    Wu SN, Chen CC, Li HF, Lo YK, Chen SA, Chiang HT. Stimulation of the BK(Ca) channel in cultured smooth muscle cells of human trachea by magnolol. Thorax 2002 Jan;57(1):67-74.
    Abstract
    
37. 
    Niitsuma T, Morita S, Hayashi T, Homma M, Oka K. Effects of absorbed components of saiboku-to on the release of leukotrienes from polymorphonuclear leukocytes of patients with bronchial asthma. Methods Find Exp Clin Pharmacol 2001 Mar;23(2):99-104.
    Abstract
    
38. 
    Homma M, Minami M, Taniguchi C, Oka K, Morita S, Niitsuma T, Hayashi T. Inhibitory effects of lignans and flavonoids in saiboku-to, a herbal medicine for bronchial asthma, on the release of leukotrienes from human polymorphonuclear leukocytes. Planta Med  2000 Feb; 66(1):88-91.
    Abstract
    

The word "natural" gets thrown around a lot in discussions of hormone replacement therapy. Premarin, for example, is widely considered to be a "natural" hormone. So is the estradiol in the estrogen "patch" and "cream" products. Triple estrogen is also considered to be a "natural" estrogen product. Are they all natural? Does it really matter? The answers depend on how you define "natural."

Triple estrogen consists of three separate estrogens — estriol, estrone, and estradiol — all of which are derived from a plant, the wild yam (Diascorea composita). How can a hormone that got its start in a vegetable be considered "natural" in the human body? The wild yam is rich in "precursor" molecules that can be easily converted by biochemists into estrogens and other steroid hormones. The molecular structure of these hormones is indistinguishable from that of the "natural" hormones produced in the human body, and as a result, they function exactly like those the body produces, especially when used in their natural proportions. Thus, the crucial variable defining "natural" is not the origin of the hormone or how it is produced, but whether its chemical structure matches that of the hormone it is intended to replace.

Premarin is Natural for Horses But Not for Humans

Premarin is widely considered by physicians to be a "natural" hormone product, because it is derived from horse urine and is not synthesized in a laboratory. But is it really natural? Certainly, it's natural in horses. But when placed in the human body, the hormones in Premarin are as foreign as any synthetic drug, because the body lacks the enzymes and cofactors to metabolize them safely.

These are composed of 100% estradiol, the most potent — and most carcinogenic — of the estrogens. The estradiol is derived from the same source as the estradiol in Triple estrogen, the wild yam, so in that sense, these products can be considered "natural." However, because they are 100% estradiol, with no estrone, and most importantly, no estriol, these products must be considered unnatural once inside the human body. The human physiology is designed to work with three forms of estrogen — estriol, estrone, and estradiol — in a ratio of about 90:7:3. Exposing the body to 100% estradiol creates an unbalanced, and therefore, unnatural and potentially dangerous situation.

Women who replace estrogen also need to replace progesterone. This may seem obvious to anyone who has studied human reproductive physiology, because estrogen and progesterone are closely linked in the normal menstrual cycle. Each month, as estrogen levels rise, progesterone levels fall, and vice versa. Unfortunately, it wasn't always so obvious to physicians and pharmaceutical companies. In the early days of ERT, tens of thousands of women developed endometrial cancer as a result of taking Premarin in the absence of progesterone. In the absence of progesterone, the estrogens in Premarin can cause excessive proliferation of endometrial tissue, which, in an alarming number of instances, can turn malignant. Progesterone largely prevents this excessive growth.

But conventional medicine being what it is, most physicians do not prescribe natural progesterone for their menopausal patients. Instead, they prescribe a synthetic progesterone-like drug, or "progestin," called Provera® (medroxyprogesterone), or one of its clones. Synthetic progestins are not the same thing as progesterone. Thanks to the pharmaceutical industry's superior promotional abilities, few physicians ever make that distinction.

Women who take Provera pay a high price for the protection it affords against Premarin-induced endometrial cancer. That price includes an increased risk of cardiovascular disease (CVD), because progestins strip away most of the protection against CVD that they gain from estrogen replacement. Since this protection is one of the main reasons they take Premarin in the first place, and since Provera causes a long list of unpleasant side effects, including breast tenderness, weight gain, depression, and breakthrough bleeding, to name just a few, you have to wonder whether they wouldn't be better off not taking anything.

Natural progesterone — which comes from the same source as the natural estrogens in triple estrogen — is a completely different story. Because it is structurally and functionally identical to the progesterone the body produces, replacing missing progesterone with natural progesterone puts back the same hormone the body is accustomed to. As a result, when used properly, natural progesterone affords the same protection against endometrial cancer as synthetic progestins, but does not interfere with estrogen's ability to protect against CVD. This was most clearly demonstrated in a large federal government-sponsored clinical trial known as PEPI (Postmenopausal Estrogen/Progestin Interventions).12

In the PEPI trial, 875 postmenopausal women were randomly placed in one of four treatment groups: 1) Placebo, 2) Estrogen (ie, Premarin) only, 3) Premarin + Provera, or 4) Premarin + natural progesterone (oral). The relevant measure was the level of HDL-cholesterol, which is known as the "good" cholesterol, since it protects against CVD. The results (Fig. 3) clearly demonstrated that when Provera was added to Premarin, HDL levels dropped nearly to baseline. By contrast, when natural progesterone was added to Premarin, there was no significant loss of HDL-based CVD protection.

If this weren't enough to recommend natural progesterone, there's also the protection it provides against osteoporosis. This ability has been most clearly shown by the work of John R. Lee, MD.13,14 Osteoporosis is the bone-thinning disease that commonly occurs following menopause. It appears to be due to a loss of both estrogen and progesterone. Replacing estrogen will usually help slow or even halt the thinning process, but it does nothing to restore bone that has already been lost.

Dr. Lee took regular bone mineral density measurements of 62 postmenopausal women who were taking either Premarin + progesterone (in a cream base) or progesterone alone for a period of at least 3 years. The women also took calcium supplements and maintained a diet and lifestyle designed to minimize bone loss. He found that natural progesterone replacement resulted in a remarkable increase in bone mineral density. Some of Dr. Lee's patients increased the density of their lumbar vertebrae by 20 to 25% in the first year! Over the 3 years of the study, the mean increase in bone mineral density was 15.4%. According to other studies, including PEPI, a 4 to 5% decrease in bone density would have been expected in women not using natural progesterone. Not surprisingly, Provera appears to provide no protection against osteoporosis and definitely does not enhance bone growth (Fig. 4).

Natural progesterone creams are widely available over-the-counter, usually at health food stores as well as mail order sources.

References:

1. 
   Schliesman B, Robinson L. Serum estrogens: quantitative analysis of the concentration of estriol compared to estradiol and estrone. Meridian Valley Laboratory. 1997;Kent, WA:Data on file.
   
2. 
   Premarin® (conjugated estrogen tablets). Wyeth-Ayerst Company. Physicians' Desk Reference, 52nd Edition. Montvale, NJ: Medical Economics Company; 1998:3111-3113.
   
3. 
   Barnes R, Lobo R. Pharmacology of Estrogens. In: Mishell D, Jr, ed. Menopause: Physiology and Pharmacology. Chicago: Year Book Medical Publishers, Inc.; 1987.
   
4. 
   Heimer G. Estriol in the postmenopause. Acta Obstet Gynecol Scand. 1987;Suppl 139:1- 23.