© Whole Foods magazine

March 2007

Pueraria mirifica: Just for Menopause or the Herb of the Decade?: Part 2

An Interview with Dr. Garry Gordon

By Richard A. Passwater, Ph.D.

 

Last month we discussed that the lowest rate of breast cancer in the known in the world was in Thailand’s northern region, where the herb Pueraria mirifica (PM) is widely used. Only PM has the unique phytoestrogen (plant estrogen), miroestrol. Miroestrol is bio-similar to estriol, an estrogen (female hormone) that is much weaker than the body’s predominant estrogen, 17ß- estradiol. Miroestrol occupies the estrogen receptors more safely. If the estrogen level is high, miroestrol will compete with receptors weakening the effect of the hormones. If the estrogen level is low, miroestrol will exert its estrogenic effect of potentiation. PM also contains several other phytoestrogens including genistein, daidzein, hydroxymiroestrol and isomiroestrol.

This month, we will discuss how PM has been shown to be safe and effective in relieving the discomforts of the “change of life” leading to menopause.

Garry F. Gordon, M.D., D.O., M.D.(H), received his doctorate of osteopathy in 1958 from the Chicago College of Osteopathy in Illinois. He received his honorary M.D. degree from the University of California Irvine in 1962 and completed his radiology residency from Mt. Zion, in San Francisco, CA, in 1964. For many years, he was the medical director of Mineral Lab in Hayward, CA, a leading laboratory worldwide for trace mineral analysis.

Dr. Gordon is co-founder of the American College for Advancement in Medicine (ACAM). He is founder/president of the International College of Advanced Longevity (ICALM) and a board member of the International Oxidative Medicine Association (IOMA). In addition, he is associated with the Gordon Research Institute, located in Payson, AZ.

 

 

Photo: Dr. Garry Gordon

 

Passwater: We have discussed that estrogens are a group of steroid compounds, named for their importance in the estrous (reproductive) cycle, and function as the primary female sex hormone. While estrogens are present in both men and women, they are usually present at significantly higher levels in women of reproductive age. The three major naturally occurring estrogens in women are estradiol, estriol and estrone. From menarche to menopause the primary estrogen is 17ß-estradiol.

What is the effect of the digestion process on miroestrol? Do breakdown products such as heterocyclic phenols more closely resemble estrogens than miroestrol itself resembles estrogens?

 

Gordon: The estrogenic hormones effective by mouth are either methylated at position 3 of the ring like Mestranol (which serves as the estrogen component in several combinations of oral contraceptives) or they have an alpha ethinyl group at position 17 like 17 alpha ethinyl estradiol. In miroestrol there is a methylene bridge between carbon 12 and 17 which may exert a similar stabilization effect in the digestive tract.

 

Passwater: Phytoestrogens naturally occur in some plants and are compounds which have estrogenic effects in animals, including humans. That is to say, phytoestrogens mimic and supplement the action of the body’s own estrogen hormones. Phytoestrogens mainly fall into the class of flavonoids: the coumestans, prenylated flavonoids and isoflavones are three of the most potent in this class. The most-researched are isoflavones, which are commonly found in soy and red clover. Lignan has also been identified as a phytoestrogen, although it is not a flavonoid.

Women know that other phytoestrogens offer some menopausal symptom relief but in most cases simply don’t do as well as desired. A study called “The Isoflavone Clover Extract (ICE) Study,” published in the Journal of the American Medical Association (JAMA) on July 9, 2003, concluded that “neither supplement had a clinically important effect on hot flashes or other symptoms of menopause.” One study may not be conclusive, but the results were not encouraging.

More recently, a study of black cohosh published in the December 2006 Annals of Internal Medicine was also discouraging [145:12; 869-879 (19 Dec 2006)]. The study’s lead author, Dr. Katherine Newton, concluded: “Black cohosh used alone or as part of a multi-botanical supplement shows little potential as an important therapy for relief of hot flashes. The yearlong study of 351 women suffering from hot flashes and night sweats found that those given black cohosh got about the same amount of relief as those who took a placebo. That’s just one study, but it is not encouraging.

Both of these recent studies are discouraging, but the body of scientific evidence does include other studies that suggest that these other phytoestrogens may have some benefit for some women over placebo effect. A more recent meta-analysis was published in January (Maturitas 55: 203-211 (2007), by Drs. L.G. Howes, J.B. Howes and D.C. Knight. This meta-analysis of several previous studies reported a statistically significant, although clinically modest effect. This study has limitations in that changes in the severity of hot flushes were not considered, only changes in the number and frequency of the flushes. Additionally, this study did not measure the effect of isoflavones on other climacteric symptoms.

What is needed, however, is a phytoestrogen with a strong positive effect in nearly all women much greater than any placebo effect. Just how “estrogen-like” are phytoestrogens and just how effective is PM?

 

Gordon: Well, you are describing PM—it has a strong positive benefit in nearly all women that far exceeds any placebo effect. In the Phase I and Phase II trials I have studied, they used all the climacteric (change of life) parameters, including hot flashes, night sweats, depression, loss of sex drive and 14 more symptoms. In every case, every woman saw immediate positive results, and after six months (the length of the trial), every woman’s score was well below the subjective level for climacteric symptoms, in all areas. But, it wasn’t until I brought some back to the United States and gave it to women here, with similar immediate results, that I became excited. I can say, after 48 years in medicine, I know a great supplement or herb when I see one. I may go so far as to say, that PM is definitely the greatest herb of the decade, and perhaps the century, and maybe even all time.

 

Passwater: As you know, Dr. Gordon, I am a biochemist and not an herbalist or physician. In addition to the nearly thousand years experience of hundreds of thousands of people, can you tell us some more about the studies?

 

Gordon: Certainly. I wouldn’t use PM in my practice if I hadn’t evaluated the literature myself. Before clinical studies of the standardized PM extract were conducted, various toxicological studies were performed. Subchronic toxicity studies were carried out by the Medicinal Herb Research Institute, Department of Medical Sciences, Ministry of Public Health.

Here’s my file copy of a couple of the clinical studies using the standardized PM extract. Dr. Alex Schauss can provide you with additional toxicological studies and the herbology of PM.

This 2001 study is “Efficacy and Safety of Pueraria mirifica (Kwao Keur Kao) for the treatment of vasomotor symptoms in perimenopausal women by Drs. V. Chandeying, S. Lamlertkittikul and A. Schauss. The other researchers beside Dr. Schauss were on the Faculty of Medicine of Prince of Songkla University and the study was conducted at the Hat Yai Center Hospital in Thailand. The clinical trial involved 37 women who took either 50 mg or 100 mg of PM over six months and found that perimenopausal women treated with PM all had significant improvement in modified Greene climacteric scale and its parameters.

 

Passwater: I see that in this study, the climacteric indicators improved (declined) as follows: hot flashes, from 2.5 to 0.5; night sweats, from 1.7 to 0.6; headaches, from 2.4 to 0.8; and mood instability, from 2.3 to 0.9. Sixteen other climacteric indicators also improved accordingly.

 

Gordon: In an earlier Phase 1 safety study, conducted by this research group in 2000 and involving ten women, it was found that, when taking 50 mg/day and 100 mg/day of PM, none of the women suffered estrogenic side effects including dysfunctional uterine bleeding, irregular menstruation or breast tenderness. The study concluded that the blood biochemistry tests established the safety of the PM. Of course, this is only a small phase-one study, and in a larger population you always expect individual differences in tolerances of anything, as well as optimal dosage, which is largely dependent on body weight. In other words, individual results may vary and any herb should be discontinued if adverse effects are noted.

I always suggest monitoring blood pressure and being alert for vaginal discharge or bleeding.

 

Passwater: In this Phase 1 study, all of the climacteric indicators declined from moderately severe (43.8) to mild (10.9). The hot flashes decreased by 11-fold, and the night sweats declined by more than four-fold, with the most significant drop occurring during the first 30 days. I’ve never seen this reported in any studies, using any other product.

So the studies show PM is very effective, but has its safety really been shown?

 

Gordon: Smith Naturals did Ames mutagenicity studies, acute, sub-chronic and chronic toxicity testing. And, when Bio-Botanica reviewed them, they further did a GLP (a lab with Good Laboratory Practices certification) toxicity test as well as a GLP Ames test to further support the testing done in Thailand. Every test returned the same result of no toxicity at normal human dosage levels and even up to more 2,000 times that dosage. Back in the 50’s, Dr. Pope conjectured from chemical models that miroestrol might enter the adverse effect range above one gram of miroestrol / dose, but that’s still more than 50 times the human dose, and no one has ever confirmed any adverse effects as Pope conjectured from chemical structural models. The standardized PM extract contains 20 mg miroestrol / 100 g. That equates to 0.2 mg / g, and since about 100 mg of PM is used per dose, the end result is 0.02 mg miroestrol / 100 mgs PM. Since Dr. Pope speculated that one gram of miroestrol could be the start of the adverse effects range, there would need to be 50 doses / day to achieve this level.

 

Passwater: Although PM has been used safely for about a thousand years by hundreds of thousands of people as an herb to keep skin young looking and help ease the natural menopause (which is a normal event in aging, not a disease) should non-pregnant, adult women take PM without medical supervision?

 

Gordon: Quite frankly, the only warning would be for women not to take PM before the age of 18. If a menstruating woman takes PM, the recommendation is not to take it during the week of her period. I have never heard of there being any consequence from taking it continuously, but Thai traditional medicine recommends younger women taking one week off. Also, I recommend very few supplements or medicines for pregnant women. There is no need for pregnant women to take PM as they are not menopausal, so I do not recommend PM for pregnant women.

 

Passwater: Focusing solely on perimenopasusal women, what is the ideal daily dosage for menopausal women?

 

Gordon: 2 mg / kg body weight. For the first month that level can be doubled. So a 150-pound woman would require 136 mg of PM / day, but could take, without any problem, 272 mg (or 3 pills / day). Most women will see relief of symptoms in a week or less. The Phase I and the Phase II trials in Thailand were on Asian women, who are normally smaller than Western women, so the dosages they used were small, compared what Western women might need. A convenient and effective regimen for American women of menopausal age would be to take 80 mg of PM twice a day.

 

Passwater: How does taking PM differ from taking so-called estrogen replacement drugs?

 

Gordon: A well-known estrogen replacement drug is produced from the urine of pregnant mares. You know how I feel about the conditions used to collect urine from these pregnant mares to make the drug, and you know how I feel about keeping the mares pregnant, year after year.

The major forms of estrogen in this popular drug are estrone (>50%), equilin (3-hydroxyestra-1,3,5,7-tetraen-17-one) (15-25%) and equienin.They are often called “conjugated equine estrogens” (CEE) because the estrogen molecules are generally present with sulfate side-groups attached. Estrone sulfate is readily converted to estradiol. It is not clear if estrogens such as equilin that are foreign to the human body have effects in women that are significantly different from the estrogens like estradiol that are normally made in the human body.

But, when this type of medicine was tested in the largest study ever done, on some 80,000 women, it was called off, as the women taking estrogen had a higher rate of heart disease and cancer than the placebo. PM, and again, standardized PM with 20 mg miroestrol / 100 g, has no side effects. We have preliminary studies on a number of types of cancer and we see PM having only beneficial effects. The same is true for bone health and circulation.

 

Passwater: Why would taking PM be safe and effective, whereas taking estrogen-related drugs, such as commonly used HRT, could be questionable?

 

Gordon: Simple. While both will alleviate symptoms associated with menopause, PM won’t harm you. If anything, it may cause you to live longer and in better health.

 

Passwater: How does taking PM differ from taking isoflavones such as genistein and daidzein?

 

Gordon: PM also contains substantial quantities of other phytoestrogens, including daidzein, genistein, puerarin, and mirificin. But most importantly, and uniquely, PM contains miroestrol.

 

Passwater: Does PM have any effect on breast size or tone?

 

Gordon: I assume you’re talking about the craze that swept the Internet, promising larger breasts in just two days. This was taken from the true story about PM enlarging breasts by a full cup size in Japan. More than a decade ago, Japanese cosmetic companies flocked to Thailand to purchase “PM” to mix in creams and to be taken orally. After some time, they sought lower and lower prices. The end result was that the wildcrafters simply mixed in less expensive species. Some Thai wildcrafters are eighth generation. They know the market value of real PM. The original breast enhancement study was done in Tokyo by Japanese Prof. Kuramoshi and Thai Assoc. Prof. Yuthana Smitasiri. They showed that 72% of women taking PM exhibited significant increases in breast size. Younger women had a markedly higher rate of success than older women, who lowered the overall success rate. Some years ago, a company in California launched ISIS, a system using real PM. They guaranteed success or your money back and had 96% satisfied customers, not asking for their money back.

 

Passwater: From my knowledge of Latin, “mirifica” means “miracle maker.” So, what other “miracles” does Pueraria mirifica make?

 

Gordon:  Well, if PM only relieved problems associated with menopause, within a week, it would already be a miracle, but there will soon be studies to show many more significant benefits from PM. One health benefit, I have already stated earlier, is that in the regions where PM grows, they have the lowest breast cancer rate in the world. Their breast cancer incidence is even 40% lower than Japan, where they consume the highest level of phytoestrogens in their daily diet (Please see Table 2 in Part 1). It’s less than 10% of the United States rate. In addition, cell culture studies show that PM is anti-cancer to estrogen-sensitive breast cancer cells. It’s even beneficial for men.

 

Passwater: Perhaps, when PM occupies estrogen receptors, it acts in the same manner as the breast cancer preventer tamoxifen in that the receptors are occupied, but not triggered to produce the cascade of chemical reactions that activate the genes that facilitate cancer growth. The mechanism of this blocking action for tamoxifen as proposed by the National Cancer Institute is shown in figures 1, 2 and 3.

Should PM be taken with any additional supplements?

 

Figure 1. The estrogen-blocking of tamoxifen. Figure courtesy of the National Cancer Institute.

 

Figure 2: Cancer-preventing compounds such as tamoxifen can fill estrogen receptors without activating cancer-promoting genes. Figure courtesy of the National Cancer Institute.

 

 

Figure 3. Estrogen receptor-filling compounds can fill the receptor without activating the cancer-promoting genes. Figure courtesy of the National Cancer Institute.

 

Gordon: A company I consult with, Longevity Plus, which produces supplements for professionals, has had very positive feedback regarding combining PM with vitamin B-12 and folic acid. I had recommended that they simply add this exciting PM herb into their proprietary B-12 formula, which alone had reportedly provided excellent support to many women, reducing fatigue, depression and irritability. Adding PM to that formula, we find, acts synergistically so that even the most difficult change of life issues that until now nothing has helped, are responding, often within two-to-four weeks. Therefore, I think PM should be combined with B-12 and folic acid.

 

Passwater: I note that PM has also traditionally been used to keep skin young-looking. What dosage do you recommend for this? Also, I note in the literature that you gave me that both men and women are taking PM as an adaptogen. Adaptogenic herbs tend to balance endocrine hormones and the immune system, and they help the body to maintain optimal homeostasis. The mechanism involving the estrogen receptors described above would indicate that PM could help to counteract the estrogen-mimic pollutants such as dioxin.

 

                Men eat the PM tuber as a food and earlier you mentioned that men take PM as well as women. How much? The same dosage for men and women?

 

Gordon: Since you’re asking about the traditional use, let me cite from a translation of the 700-year-old Thai palm leaves:

* Take the tuberous root of Pueraria with big leaves, pound and blend with cow’s milk. The benefits of this medicine is to support memory, talk big, and be able to remember three books of the astrology, make the skin smooth like a six year old kid, live a very long life and parasite diseases are not able to be of trouble.

* Blend with rice milk by keeping the rice milk until sour, the benefit is to support softening skin, as the skin of the angel.

* Blend with butter cream or honey, the benefits are to support long life, memory and ability to remember three books and the ability for entertaining a thousand customers.

* Blend with yogurt, the benefits are to support long life, dark hair, strong teeth and anti skin wrinkles.

* Bleach with buffalo milk, apply to the hair for support as a hair tonic, the gray hair will become dark, use with sesame oil for the benefits of darkening hair, and support of hair growth, smoothening skin, every type of parasite disease is not able to be of trouble.

Clearly, PM was meant here for men as well as women. The dosage for men is half that of women, so 1 mg / kg body weight. This dosage was first calculated from the dosing of “peppers” as used in Thai traditional medicine. Smith Naturals worked with Dr. Schauss for six months, collecting samples and analyzing the miroestrol levels, to convert the traditional pepper dose into milligram dosing.

 

Passwater:  Does PM affect male breasts?

 

Gordon:  I had to think about this, as the male breast has the same estrogen receptors as women. Since men don’t have the same amount of mammary tissue, the answer has to be no, or at least not in the same way as PM has been shown to increase breast size and breast firmness in women.

 

Passwater: Does PM have a positive longevity effect or does it just make people look younger?

 

Gordon: The old men and women who’ve taken it regularly, in the north of Thailand, have natural black hair well into their 80s. Old women enjoy chasing after their young grandchildren and men still hike in to the mountains, running up hills much like a jack rabbit. These women still have firm breasts and young skin. Men pursue active sex lives. They have great memories and don’t remember ever being sick. We interviewed Sam, a man in his 80s, who sleeps through the night and didn’t understand why we would ask if he woke to urinate. He said, “no one here wakes up to do that.”

 

Passwater: Well, Dr. Gordon, you certainly have gotten my attention about the health benefits of the herb Pueraria mirifica (PM). In the meantime, let’s take a break and come back to discuss RNAi in a few months. Thanks for sharing your knowledge with our readers once again. WF

 

© 2007 Whole Foods Magazine and Richard A. Passwater, Ph.D.

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