HRT Plus® ─ Medicinal Miracle in a Pill

HRT Plus® ─ Medicinal Miracle in a Pill

The Thai medicinal plant, Pueraria mirifica, was appropriately named ─ the second half of its botanical designation means “achieving wonderful things, or working wonders.”  Used in Thailand for hundreds of years as a rejuvenating tonic for both men and women, an abundance of medical research over the past half century has revealed P. mirifica’s multifaceted therapeutic actions, from safely alleviating menopausal symptoms without the need for toxic drugs, to supporting cardiovascular, bone, and neurological health, to combating oxidation, protecting against cancer, and even potentially promoting longevity. Now, the “miracle” herb P. mirifica is available in a standardized formulation called HRT Plus® ─ “Herbal Remedy from Thailand.” Let’s take a look at the health benefits for both men and women of this time-proven, clinically-tested, and remarkable herb.

Phytoestrogen-rich P. mirifica

P. mirifica, also known as “Kwao Kruea Khao,” is a medicinal plant in the legume family indigenous to Thailand. Its tuberous root is rich in phytoestrogens, botanical compounds with structural and functional similarity to estrogens produced in the body, that are also found in other sources such as soy, red clover, flaxseed, and black cohosh. A 2012 study identified at least 17 P. mirifica phytoestrogens, (1) including isoflavones such as genistin, genistein, daidzein, and puerarin; coumestrans; and the unique compounds miroestrol and its analogs (including deoxymiroestrol). Miroestrol is a potent phytoestrogen, (2) similar in chemical structure to estriol (one of the three major human estrogens), and possesses higher estrogenic activity than most other phytoestrogens.

P. mirifica Components Act as Naturally-Occurring “SERM’s”

Miroestrol and deoxymiroestrol are in a class of compounds that medical researchers call SERM’s ─ selective estrogen receptor modulators; (3) that is, they selectively interact with estrogen receptors (ER’s) to produce a range of beneficial tissue-specific effects. (Estrogens exert their physiological actions by binding to ER’s located within cells of target tissues, such as breast, uterus, brain, bone, heart, etc. There are two subtypes of ER’s, known as ERalpha and ERbeta.) In some tissues (breasts, uterine endometrium, etc.), they bind to ERalpha’s to block excessive stimulation by stronger hormones such as estrone and estradiol that can lead to breast, endometrial, or other estrogen-dependent cancers; in other tissues (brain, bone, heart, etc.) they activate ERbeta’s to potentiate the effect of estrogen in supporting bone density, cardiovascular, and neurological health, and relieving menopausal symptoms. SERM’s do not alter hormone levels or production; rather, their mechanism of action is through either inhibition or activation of ER’s, with the overall effect of moderating or normalizing estrogenic effects.

In recent years, SERM’s have been the subject of considerable research directed at their use as an alternative to conventional hormone replacement therapy (HRT) for the treatment of menopausal symptoms. When results of the Women's Health Initiative and other large studies demonstrated that the use of Premarin® (conjugated equine estrogens isolated from the urine of pregnant mares) and Provera® (medroxyprogesterone acetate, a synthetic progesterone) caused startling increases in risks of breast cancer, venous thromboembolism (blood clot within a vein), stroke, and heart disease, (4-6) it was clear that alternative safe and effective therapies are needed. (This medical wake-up call was no surprise, considering that neither equine estrogens such as equilin and equilenin, nor synthetic progesterone are bio-identical to human hormones. Also, the ethical questions raised by the Premarin® manufacturing process alone should have discouraged use of this deficient drug.) P. mirifica, on the other hand, has been demonstrated in clinical trials to be a safe, non-toxic, and effective alternative to conventional HRT. Even long before clinical proof of its efficacy was established, it had been used by menopausal women in Thailand and the East to alleviate their symptoms.

But P. mirifica is not just indicated for relief from menopausal complaints; as we’ll see, its therapeutic potential is huge. Dozens of studies in cell lines, animals, and humans, have evaluated phytoestrogen-rich P. mirifica’s wide spectrum of beneficial actions that also include support of cardiovascular, neurological and bone health; antioxidant and antiproliferative (anti-cancer) action; and perhaps most intriguingly, its impact on cell replication and potentially, longevity. Let’s first examine results of studies establishing P. mirifica as a superior and effective treatment for menopausal symptoms.

P. mirifica Provides Side-Effect-Free Menopause Relief

Several studies have all confirmed the efficacy of P. mirifica in relieving symptoms such as hot flashes, night sweats, depression, etc. Most of these studies used a modified rating system known as the Greene climacteric scale to gauge symptoms. In three separate studies, women who had received between 25 and 100 mg of P. mirifica daily for six months experienced a reduction in menopausal complaints from severe to mild, as shown by decreases in climacteric indicators. (7-9) One study specifically evaluated its efficacy in alleviating a common symptom, vaginal dryness and atrophy, at daily doses between 20 to 50 mg for six months, with positive results. (10) A revealing Phase III study compared the efficacy of P. mirifica versus conjugated equine estrogen (Premarin®) in treating hot flashes, night sweats, urogenital, and psychological symptoms. Sixty perimenopausal women received either 50 mg P. mirifica or 0.625 mg Premarin® (with or without 2.5 mg medroxyprogesterone acetate (Provera®)) for six months. Both groups obtained equivalent symptom relief, with no statistically significant difference between groups, as determined by the climacteric scale. Researchers concluded, “P. mirifica, containing phytoestrogens, has estrogenic effect[s] similar to conjugated equine estrogens and can alleviate climacteric symptoms in perimenopausal women.  P. mirifica demonstrates great promise in the treatment of climacteric symptoms." (11)

What the authors of this last study didn’t say was that P. mirifica relieves these symptoms without causing the breast cancer, heart disease or blood clots associated with standard HRT; quite the opposite, P. mirifica alleviates menopausal symptoms while at the same time countering breast cancer and promoting cardiovascular health (as well as a full range of other beneficial actions). P. mirifica at the recommended human dosage is very safe, with minimal side effects. According to one group of researchers, extrapolating from animal toxicology studies, the lethal dose for a 50 kg (110 pound) woman would be on the order of 800 g of the plant extract (7) (that’s almost two pounds, an inconceivable amount to ingest!).

P. mirifica Protects against Cancer, Cardiovascular disease, and Osteoporosis

The incidence of cardiovascular disease and osteoporosis increases with advancing age and post-menopausal women appear to be particularly at risk for developing these conditions. (12) Increasing risk of breast cancer is another concern for women as they age. (13) P. mirifica has been shown to protect against all of these conditions. Its antiproliferative action on breast cancer cells was demonstrated in an animal study in which it lowered the incidence of chemically induced mammary tumors through binding of its phytoestrogens to ERalpha. (14) P. mirifica also has beneficial effects on the cardiovascular system by improving endothelial function (the endothelium is the lining of blood and lymphatic vessels) (5) and normalizing lipid metabolism. (12) In a double-blind, placebo-controlled clinical trial, 19 postmenopausal women received either P. mirifica powder or placebo. After two months of treatment, the P. mirifica group showed significant increases in serum high-density lipoprotein (“good” cholesterol) and decreases in low-density lipoprotein (“bad” cholesterol). Researchers determined that these improvements in lipid metabolism result from selective binding of P. mirifica phytoestrogens to ERalpha and ERbeta. (12) Furthermore, animal and human studies show that P. mirifica positively impacts bone health by promoting bone formation and suppressing bone loss. (6;15-17) A human double-blind placebo-controlled study on 71 post-menopausal women showed that varying doses of P. mirifica (20 to 50 mg per day) for six months produced an estrogen-like beneficial effect on bone turnover rate (the rate of bone formation to bone resorption of the skeleton) without affecting breast tissue, endometrial thickness or serum estradiol level (6) (in contrast to synthetic HRT which has a proliferating effect on the uterine lining and breast tissue).

P. mirifica Provides Antioxidant and Neuroprotective Support

In mice, P. mirifica and its constituent miroestrol have been shown to improve activities of the antioxidant enzymes superoxide dismutase and catalase, raise levels of several forms of glutathione, and reduce lipid peroxidation. (2,18) One study found that P. mirifica demonstrates antioxidant activity and neuroprotective potential against glutamate toxicity in mouse hippocampal neurons. (Neuronal degeneration results from oxidative stress and excessive activation of glutamate receptors in the brain.) These favorable effects on brain cells are due to the scavenging activity of P. mirifica constituents against peroxide and related reactive oxygen species. (19) Besides oxidative stress, neurodegeneration can also be caused by a loss of connections between neurons, a process that can be countered by P. mirifica. In cultured rat hippocampal neurons, P. mirificawas shown to increase synaptic density (the formation of synapses) through an ER-mediated pathway, (20) another mechanism for its neuroprotective effects.

Last but not Least: P. mirifica Constituent Puerarin Activates Telomerase

In a fascinating 2008 study, researchers demonstrated that a major P. mirifica isoflavone, puerarin, increases the activity of telomerase (an enzyme involved in cellular replication), a finding that ultimately may have important implications for promoting optimal health and longevity. Telomerase adds DNA repeats to telomeres, the protective “caps” at the ends of chromosomes, each time a cell divides.  Most of the body’s cells (excluding reproductive cells) can divide only a finite number of times due to a programmed genetic clock associated with decreased telomerase production over time, leading to shortened telomeres and arrested cell division. This process, known as replicative senescence, ultimately results in aging and age-related diseases. What researchers discovered was that puerarin dose-dependently increases telomerase activity and delays the onset of senescence in specialized cultured cells. (21) Cells that had previously not survived in culture due to the onset of replicative senescence instead proliferated and formed colonies in the presence of telomerase-activating puerarin. In other words, the P. mirifica-incubated cells were endowed with enhanced cell-division potential, and therefore, increased longevity. An intriguing topic for future research would be the effect of puerarin on prolonging life span.

According to physician and researcher Dr. Garry Gordon, who has studied the benefits of P. mirifica and uses it with excellent results in his practice, the lowest rate of breast cancer in the world is in northern Thailand, where it is consumed on a regular basis. The region also boasts low incidence of other diseases when compared with other parts of the world. Dr. Gordon has observed the longevity, vitality, and youthful demeanor of people in the north of Thailand: “The old men and women, who’ve taken it regularly, in the north of Thailand, have natural black hair well into their 80’s. Old women enjoy chasing after their young grandchildren and men still hike into the mountains, running up hills. The women still have firm breasts and young skin, and men pursue active sex lives [and so must the women!]. They have great memories and don’t remember ever being sick.”

All of the benefits of this extraordinary plant, from alleviation of menopausal symptoms to longevity enhancement, are now available in the product HRT Plus®. (Please do not confuse the “HRT” in the product’s name ─ which stands for “Herbal Remedy from Thailand” ─ with dangerous synthetic Hormone Replacement Therapy.) The product is standardized to contain 0.02 mg miroestrol/100 mg dose of P. mirifica and also contains co-factors B-12 (methylcobalamin), folic acid, B6, and biotin for additional support. And while HRT Plus® provides safe and effective relief from menopausal symptoms, it is not limited to this indication: P. mirifica is a botanical powerhouse suitable for both men and women that protects the brain, heart, and bones; fights oxidation and cancer; promotes vitality and most likely, longevity. The recommended dosage for women (depending on symptom relief and response) is one to two tablets daily; the dose for men is one tablet daily. Now you can reap all of the benefits of this miraculous plant extract with HRT Plus!

References

1.  Malaivijitnond S. Medical applications of phytoestrogens from the Thai herb Pueraria mirifica. Front Med. 2012 Mar;6(1):8-21.

2.  Jearapong N, Chatuphonprasert W, Jarukamjorn K. Miroestrol, a phytoestrogen from Pueraria mirifica, improves the antioxidation state in the livers and uteri of β-naphthoflavone-treated mice. J Nat Med. 2013 Jun 28.

3. Pueraria mirifica and the Treatment of Menopausal Symptoms- AARM Reference Review. Journal of Restorative Medicine. 2012; 1: 91-95.

4. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women - Principal results from the Women’s Health Initiative randomized controlled trial. Jama-Journal of the American Medical Association. 2002; 288(3):321-333.

5. Wattanapitayakul SK, Chularojmontri L, Srichirat S. Effects of Pueraria mirifica on vascular function of ovariectomized rabbits. J Med Assoc Thai. 2005 Jun;88 Suppl 1:S21-9.

6. Manonai J, Chittacharoen A, Udomsubpayakul U, Theppisai H, Theppisai U. Effects and safety of Pueraria mirifica on lipid profiles and biochemical markers of bone turnover rates in healthy postmenopausal women. Menopause. 2008 May-Jun;15(3):530-5.

7. Chandeying V, Lamlertkittikul S. Challenges in the conduct of Thai herbal scientific study: efficacy and safety of phytoestrogen, Pueraria mirifica (Kwao Keur Kao), phase I, in the alleviation of climacteric symptoms in perimenopausal women. J Med Assoc Thai. 2007 Jul;90(7):1274-80.

8. Lamlertkittikul S, Chandeying V. Efficacy and safety of Pueraria mirifica (Kwao Kruea Khao) for the treatment of vasomotor symptoms in perimenopausal women: Phase II Study. J Med Assoc Thai. 2004 Jan;87(1):33-40.

9. Virojchaiwong P, Suvithayasiri V, Itharat A. Comparison of Pueraria mirifica 25 and 50 mg for menopausal symptoms. Arch Gynecol Obstet. 2011 Aug;284(2):411-9.

10.  Manonai J, Chittacharoen A, Theppisai U, Theppisai H. Effect of Pueraria mirifica on vaginal health. Menopause. 2007 Sep-Oct;14(5):919-24.

11. Chandeying V, Sangthawan M. Efficacy comparison of Pueraria mirifica (PM) against conjugated equine estrogen (CEE) with/without medroxyprogesterone acetate (MPA) in the treatment of climacteric symptoms in perimenopausal women: phase III study. J Med Assoc Thai. 2007 Sep;90(9):1720-6.

12. Okamura S, Sawada Y, Satoh T, et al. Pueraria mirifica phytoestrogens improve dyslipidemia in postmenopausal women probably by activating estrogen receptor subtypes. Tohoku J Exp Med. 2008 Dec;216(4):341-51.

13. Moser M, Patnick J, Beral V. Do women know that the risk of breast cancer increases with age? Br J Gen Pract. 2007 May 1; 57(538): 404–406.

14. Cherdshewasart W, Panriansaen R, Picha P. Pretreatment with phytoestrogen-rich plant decreases breast tumor incidence and exhibits lower profile of mammary ERalpha and ERbeta. Maturitas. 2007 Oct 20;58(2):174-81.

15. Udomsuk L, Chatuphonprasert W, Monthakantirat O, Churikhit Y, Jarukamjorn K. Impact of Pueraria candollei var. mirifica and its potent phytoestrogen miroestrol on expression of bone-specific genes in ovariectomized mice.  Fitoterapia. 2012 Dec;83(8):1687-92.

16. Tiyasatkulkovit W, Charoenphandhu N, Wongdee K, Thongbunchoo J, Krishnamra N, Malaivijitnond S. Upregulation of osteoblastic differentiation marker mRNA expression in osteoblast-like UMR106 cells by puerarin and phytoestrogens from Pueraria mirifica. Phytomedicine. 2012 Oct 15;19(13):1147-55.

17. Urasopon N, Hamada Y, Cherdshewasart W, Malaivijitnond S. Preventive effects of Pueraria mirifica on bone loss in ovariectomized rats. Maturitas. 2008 Feb 20;59(2):137-48.

18. Chatuphonprasert W, Udomsuk L, Monthakantirat O, Churikhit Y, Putalun W, Jarukamjorn K. Effects of Pueraria mirifica and miroestrol on the antioxidation-related enzymes in ovariectomized mice. J Pharm Pharmacol. 2013 Mar;65(3):447-56.

19. Sucontphunt A, De-Eknamkul W, Nimmannit U, Dan Dimitrijevich S, Gracy RW. Protection of HT22 neuronal cells against glutamate toxicity mediated by the antioxidant activity of Pueraria candollei var. mirifica extracts. J Nat Med. 2011 Jan;65(1):1-8.

20. Chindewa R, Lapanantasin S, Sanvarinda Y, Chongthammakun S. Pueraria mirifica, phytoestrogen-induced change in synaptophysin expression via estrogen receptor in rat hippocampal neuron. J Med Assoc Thai. 2008 Feb;91(2):208-14.

21. Zhu J, Wang X, Shang Y, et al. Puerarin reduces endothelial progenitor cells senescence through augmentation of telomerase activity. Vascul Pharmacol. 2008 Aug-Sep;49(2-3):106-10.