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Friday, 1 May 2015

The Holistic prevention, management and treatment of Polycystic Ovarian Syndrome: The Fertility Herb Red Clover

By Kyle J. Norton Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.


                    Polycystic Ovarian Syndrome


Polycystic Ovarian Syndrome is defined as endocrinologic diseases among reproductive-age women caused by undeveloped follicles clumping on the ovaries that interferes with the function of the normal ovaries associated with a high risk for metabolic disorder(1) as resulting of enlarged ovaries(2), leading to hormone imbalance(excessive androgen and anti-müllerian hormone (AMH) )(1)(3)(4)(5), induced Hirsutism(6)(7), reproductive disorder(10(12)), risks of type 2 diabetes(9)(10)(11), metabolic syndrome(10)(12) and early cardiovasular disease(8)(13), acne(10)(14), endometrial cance(18)(19),weight gain and obesity(15)(16)(17). The syndrome effects over 5% of women population or 1 in 20 women.
Unfortunately, according to studies, women with PCOs after the reproductive age, are associated to  continuously increase risk of type II diabetes, with no increasing altered glucose tolerance(20), CVD and hypertension(21).

The prevention and management  In Herbal Medicine


Polycystic ovary syndrome (PCOS) is unpreventable in Western medicine. Early diagnosis and treatment  may reduce risk of its complications, including infertility, metabolic syndrome, obesity, diabetes, cardiovascular diseases, stroke, etc.
        Reduce fat intake less than 30% of total calories with a low proportion of saturated fat and high in fiber from predominantly low-glycaemic-index-carbohydrate foods for patients with PCOs(827a). Calorie intake should be distributed between several meals per day with restricted intake of snacks and drinks(828).

                    The Fertility Herb: Red Clover


Red clover is an herbaceous, perennial plant, native to Europe, western Asia and northwest Africa, used traditional in treating whooping cough(945), respiratory problems, and skin inflammations(945). menopause symptoms(945)(946)(947) and inflammatory diseases such as atherosclerosis and cardiovascular disease(944) by purifying the blood and clearing mucus from the lungs(948).

1. Isoflavones
Red clover contains isoflavonoid, one type of phytoestrogen used in regulating the levels of estrogen in the body by occupying the estrogen receptor site(949)(950)(951), through its estrogenic(951) and anti estrogenic(952) effects in hormonal balancing for a better chance for fertility(953).

2. Neuroprotective effects
Formononetin (FMNT), an isoflavone found  in red clover may be next potential candidate used for neurodegenerative disorders(958)(959) in central nervous system as it significantly attenuated the cell loss induced by induced by N-methyl-D-asparate (NMDA) in primary-cultured cortical neurons, according to the study by Fourth Military Medical University, Xi'an(954). On central nervous system, the herb also was found effective in improve anxiety(955)(856), profuse sweating, insomnia, memory loss, decreased sexual drives(956), depression(957), etc.

3. Metabolic syndrome(967)
Women with PCOs are associated to increased risk metabolic syndrome such as metabolic syndrome risk factors high blood pressure, obesity, high cholesterol, and insulin resistance. Intake of red clover has shown effectively in reduced total serum cholesterol and low-density lipoprotein (LDL) cholesterol levels, triglyceride levels,  and increased high-density lipoprotein (HDL) cholesterol(960)(961), lowered cardiovascular risk(962)(963), improved obesity(964) and insulin resistance(965)(966).

4. The weight loss vitamin C
Vitami C found abundantly in red clover has shown strong evidneces epidemiologically in reducing weight loss for obese population, espexially for obese women with PCOs.

See The weight loss vitamin C for more details
[Vitamin C  and other nutrients deficiency not only is associated to the risk of Obesity(807) but also enhances the risk of lipids, inflammation and insulin resistance(808).
According to the research team at Universidad Autónoma de Querétaro, there is an associated link between Obesity and  Zinc and vitamins A and C concentration in in women from rural Mexico, in a fasting blood sample analysis (809).
Although genetic susceptibility to obesity is associated with gene polymorphisms affecting biochemical pathways which also impacted by specific foods and nutrients. According to Dr. Johnston CS., vitamin C depletion is associated to positively related to body mass, individuals with adequate vitamin C status oxidize 30% more fat during a moderate exercise bout than individuals with low vitamin C status(810)

Vitamin C, the protective effect against obesity
Endothelial dysfunction has found to be associated to the incidence of obesity(811). The study of 76 healthy subjects (50 men and 26 women aged 21-45 years) obese subject, showed a positive effect of vitamin C and indomethacin in reduced oxidative stress contributed to endothelial dysfunction in human obesity(812).
In the evaluation of the potential inhibitory activity on α-glucosidase and pancreatic lipase by Citrus spp. fruits of Spanish origin, grapefruit, contained higher contents of phytochemicals such as vitamin C, is found to have a great value for nutrition and treatment of diet-related diseases(813).
L-Ascorbic acid in the study, whether  would facilitate the anti-obesity effects of chitosan and psyllium husk in vivo, showed addition of vitamin C in diet  influenced the reduction in body weight gain and food efficiency ratio, and the increase in total fecal weight and fecal fat excretion in guinea pigs fed a high-fat diet(814)]

5. Immunity 
Epidemiological studies suggested that red clover processes tenacious anti oxidant(968)(969) and anti inflmmatory(970)(971) effects in fighting against bacterial and viral infection(972)(973) and inflammation(974), free radical(975)(976) causes of irregular cell growth(970)(977) and protecting DNA integrity(979).


Side effects
1. There are no side effects from red clover, but people takes the herb for the first time may experience headache, nausea, and rash(980).
2. Do not use red clover during pregnancy as the herb may increase the risk for vaginal prolapse before the term(981)
3. Risk of bleeding due to its anticoagulant effects(982).

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References
(1) Adiposity and metabolic dysfunction in polycystic ovary syndrome by Sam S.(PubMed)
(2) A "kiss" before conception: triggering ovulation with kisspeptin-54 may improve IVF by Young SL.(PubMed)
(3.) Androgen hyperfunction and excessive heterosexual hair growth in women, with special attention to the polycystic ovarian syndrome by Lunde O1.(PubMed)
(4) Expression of anti-Müllerian hormone in letrozole rat model of polycystic ovary syndrome by Du DF1, Li XL, Fang F, Du MR.(PubMed)
(5) [Serum levels of anti-muller hormone in women with polycystic ovary syndrome and healthy women of reproductive age].[Article in Bulgarian] by Parahuleva N, Pehlivanov B, Orbecova M, Deneva T, Uchikova E.(PubMed)
(6) [Current opinions on the etiology and pathophysiology of hirsutism].[Article in Polish] by Krysiak R1, Kedzia A, Okopień B.(PubMed)
(7) The clinical evaluation of hirsutism by Somani N1, Harrison S, Bergfeld WF.(PubMed)
(8) Polycystic ovary syndrome and insulin: our understanding in the past, present and future by Mayer SB1, Evans WS, Nestler JE.(PubMed)
(9) Association of mean platelet volume with androgens and insulin resistance in nonobese patients with polycystic ovary syndrome by Dogan BA1, Arduc A2, Tuna MM1, Karakılıc E1, Dagdelen I1, Tutuncu Y1, Berker D1, Guler S1.(PubMed)
(10) Approach to the patient: contraception in women with polycystic ovary syndrome by Yildiz BO1.(PubMed)
(11) Polycystic ovarian syndrome (PCOS): a significant contributor to the overall burden of type 2 diabetes in women by Talbott EO1, Zborowski JV, Rager JR, Kip KE, Xu X, Orchard TJ.(PubMed)
(12) Prevalence of vitamin D deficiency in Slovak women with polycystic ovary syndrome and its relation to metabolic and reproductive abnormalities by Figurová J1, Dravecká I, Javorský M, Petríková J, Lazúrová I.(PubMed)
(13) Role of Insulin Sensitizers on Cardiovascular Risk Factors in Polycystic Ovarian Syndrome: A Meta-Analysis by Thethi TK1, Katalenich B2, Nagireddy P3, Chabbra P4, Kuhadiya N5, Fonseca V1.(PubMed)
(14) Acne in hirsute women by Lumezi BG1, Pupovci HL1, Berisha VL1, Goçi AU2, Gerqari A3.(PubMed)
(15) Obesity and polycystic ovary syndrome by Naderpoor N1, Shorakae S, Joham A, Boyle J, De Courten B, Teede HJ.(PubMed)
(16) Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan by Teede H1, Deeks A, Moran L.(PubMed)
(17) Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome. by Whigham LD1, Butz DE2, Dashti H3, Tonelli M3, Johnson LK1, Cook ME2, Porter WP4, Eghbalnia HR5, Markley JL6, Lindheim SR7, Schoeller DA8, Abbott DH9, Assadi-Porter FM10.(PubMed)
(18) Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis by Barry JA1, Azizia MM1, Hardiman PJ2.(PubMed)
(19) Risk of cancer among women with polycystic ovary syndrome: a Danish cohort study by Gottschau M1, Kjaer SK2, Jensen A1, Munk C1, Mellemkjaer L3.(PubMed)
(20) Polycystic ovary syndrome: metabolic consequences and long-term management by Carmina E1.(PubMed)
(21) Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype by Armeni E1, Stamatelopoulos K, Rizos D, Georgiopoulos G, Kazani M, Kazani A, Kolyviras A, Stellos K, Panoulis K, Alexandrou A, Creatsa M, Papamichael C, Lambrinoudaki I.(PubMed)
(827a) Diet and nutrition in polycystic ovary syndrome (PCOS): pointers for nutritional management by Farshchi H, Rane A, Love A, Kennedy RL(PubMed)
(828) The optimal diet for women with polycystic ovary syndrome? by Marsh K, Brand-Miller J.(PubMed

(944) Red clover extract: a source for substances that activate peroxisome proliferator-activated receptor alpha and ameliorate the cytokine secretion profile of lipopolysaccharide-stimulated macrophages by Mueller M1, Hobiger S, Jungbauer A.(PubMed)
(945) The University of Maryland medical  center
(946) Effectiveness of red clover in alleviating menopausal symptoms: a 12-week randomized, controlled trial by Shakeri F1, Taavoni S, Goushegir A, Haghani H.(PubMed)
(947) Black cohosh (Cimicifuga spp.) for menopausal symptoms by Leach MJ1, Moore V.(PubMed)
(948) Trifolium pratensen, Phytochemicals by Martina Trossello
(949) [Estrogen-effective isoflavones in Trifolium pratense (red clover). Distribution in superterranean parts of plants and occurrence as "bound" isoflavones].[Article in German]by Schultz G.(PubMed)
(950) Effect of soy isoflavones on endometriosis: interaction with estrogen receptor 2 gene polymorphism. by Tsuchiya M1, Miura T, Hanaoka T, Iwasaki M, Sasaki H, Tanaka T, Nakao H, Katoh T, Ikenoue T, Kabuto M, Tsugane S.(PubMed)
(951) Isoflavones: estrogenic activity, biological effect and bioavailability by Vitale DC1, Piazza C, Melilli B, Drago F, Salomone S.(PubMed)
(952) Phytochemistry and biological properties of glabridin by Simmler C1, Pauli GF, Chen SN.(PubMed)
(953) Recovery of normal fertility after grazing on oestrogenic red clover by Morley FH, Axelsen A, Bennett D.(PubMed)
(954) Neuroprotective effects of formononetin against NMDA-induced apoptosis in cortical neurons by Tian Z1, Liu SB, Wang YC, Li XQ, Zheng LH, Zhao MG.(PubMed)
(955) Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts by Lipovac M1, Chedraui P, Gruenhut C, Gocan A, Stammler M, Imhof M.(PubMed)
(956) A review of non-hormonal options for the relief of menopausal symptoms by Albertazzi P1.(PubMed)
(957) [Feminorm good night to treat the menopause].[Article in Bulgarian] by Malinova M.(PubMed)
(958) The isoflavones mixture from Trifolium pratense L. protects HCN 1-A neurons from oxidative stress by Occhiuto F1, Palumbo DR, Samperi S, Zangla G, Pino A, De Pasquale R, Circosta C.(PubMed)
(959) The phytoestrogenic isoflavones from Trifolium pratense L. (Red clover) protects human cortical neurons from glutamate toxicity by Occhiuto F1, Zangla G, Samperi S, Palumbo DR, Pino A, De Pasquale R, Circosta C.(PubMed)
(960) Influence of red clover-derived isoflavones on serum lipid profile in postmenopausal women by Terzic MM1, Dotlic J, Maricic S, Mihailovic T, Tosic-Race B.(PubMed)
(961) Effect of Trifolium pratense-derived isoflavones on the lipid profile of postmenopausal women with increased body mass index by Chedraui P1, San Miguel G, Hidalgo L, Morocho N, Ross S.(PubMed)
(962) Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women by Nestel PJ1, Pomeroy S, Kay S, Komesaroff P, Behrsing J, Cameron JD, West L.(PubMed)
(963) Isoflavones reduce arterial stiffness: a placebo-controlled study in men and postmenopausal women by Teede HJ1, McGrath BP, DeSilva L, Cehun M, Fassoulakis A, Nestel PJ.(PubMed)
(964) Dried Pomegranate Potentiates Anti-Osteoporotic and Anti-Obesity Activities of Red Clover Dry Extracts in Ovariectomized Rats by Kang SJ1,2, Choi BR3, Kim SH4, Yi HY5, Park HR6, Kim DC7, Choi SH8, Han CH9, Park SJ10,8, Song CH10,8, Ku SK11,12, Lee YJ13,14.(PubMed)
(965) Effect of oral phytoestrogen on androgenicity and insulin sensitivity in postmenopausal women by Lee CC1, Bloem CJ, Kasa-Vubu JZ, Liang LJ.(PubMed)
(966) Effects of supplementation with purified red clover (Trifolium pratense) isoflavones on plasma lipids and insulin resistance in healthy premenopausal women by Blakesmith SJ1, Lyons-Wall PM, George C, Joannou GE, Petocz P, Samman S.(PubMed)
(967) Phytoestrogens and the metabolic syndrome by Jungbauer A1, Medjakovic S.(PubMed)
(968) Effect of red clover-derived isoflavone supplementation on insulin-like growth factor, lipid and antioxidant status in healthy female volunteers: a pilot study by Campbell MJ1, Woodside JV, Honour JW, Morton MS, Leathem AJ.(PubMed)
(969) Research on antioxidant effects and estrogenic effect of formononetin from Trifolium pratense (red clover) by Mu H1, Bai YH, Wang ST, Zhu ZM, Zhang YW.(PubMed)
(970) Trifolium species-derived substances and extracts--biological activity and prospects for medicinal applicationsby Kolodziejczyk-Czepas J1.(PubMed)
(971) Biochanin-A, an isoflavon, showed anti-proliferative and anti-inflammatory activities through the inhibition of iNOS expression, p38-MAPK and ATF-2 phosphorylation and blocking NFκB nuclear translocation by Kole L1, Giri B, Manna SK, Pal B, Ghosh S.(PubMed)
(972) Trifolium pratense L. as a potential natural antioxidant by Vlaisavljevic S1, Kaurinovic B2, Popovic M3, Djurendic-Brenesel M4, Vasiljevic B5, Cvetkovic D6, Vasiljevic S7.(PubMed)
(973) Antibacterial activity of leaves extracts of Trifolium alexandrinum Linn. against pathogenic bacteria causing tropical diseases by Khan AV1, Ahmed QU, Shukla I, Khan AA.(PubMed)
(974) Anti-HIV, anti-poxvirus, and anti-SARS activity of a nontoxic, acidic plant extract from the Trifollium species Secomet-V/anti-vac suggests that it contains a novel broad-spectrum antiviral by Kotwal GJ1, Kaczmarek JN, Leivers S, Ghebremariam YT, Kulkarni AP, Bauer G, De Beer C, Preiser W, Mohamed AR.(PubMed)
(975) Free radical scavenging actions of three Trifolium species in the protection of blood plasma antioxidant capacity in vitro by Kolodziejczyk-Czepas J1, Nowak P, Moniuszko-Szajwaj B, Kowalska I, Stochmal A.(PubMed)
(976) Biological activity of clovers - free radical scavenging ability and antioxidant action of six Trifolium species by Kolodziejczyk-Czepas J1, Nowak P, Kowalska I, Stochmal A.(PubMed)
(977) Ester and carbamate ester derivatives of Biochanin A: synthesis and in vitro evaluation of estrogenic and antiproliferative activities by Fokialakis N1, Alexi X, Aligiannis N, Siriani D, Meligova AK, Pratsinis H, Mitakou S, Alexis MN.(PubMed)
(978) Formononetin induces apoptosis in PC-3 prostate cancer cells through enhancing the Bax/Bcl-2 ratios and regulating the p38/Akt pathway by Zhang X1, Bi L, Ye Y, Chen J.(PubMed)
(979) The red clover (Trifolium pratense) isoflavone biochanin A modulates the biotransformation pathways of 7,12-dimethylbenz[a]anthracene by Chan HY1, Wang H, Leung LK.(PubMed)
(980) Red clover(WebMD)
(981) Fertility and growth of nulliparous ewes after feeding red clover silage with high phyto-oestrogen concentrations by Mustonen E1, Taponen S1, Andersson M1, Sukura A2, Katila T1, Taponen J1.(PubMed)
(982) [Oral anticoagulants and medicinal plants. An emerging interaction].[Article in Italian] by Argento A1, Tiraferri E, Marzaloni M.(PubMed)