• Red Clover
    Red Clover
  • Red Clover
    Red Clover

Red Clover

RED CLOVER IFL 40 (USP)

USP
DMF

Linnea extracts and manufactures Red Clover as a botanical ingredient for dietary supplement purposes.

Menopause has only recently been widely recognised by the medical profession as a medical condition manifested by a variety of unpleasant symptoms that may also contribute to the development of other chronic conditions [1]. Epidemiological studies suggest that the low incidence of menopausal symptoms and correlated diseases in Asian women is directly correlated with the high content of food rich in isoflavone phytoestrogens in their diet [2].

Isoflavones are dietary phytoestrogens capable of producing estrogenic effects. They are present in extremely variable concentrations in food in a wide number of forms of which Formononetin, Biochanin, Daidzein and Genistein are the most commonly occurring biologically active forms.

Isoflavone are present in pulse-based foods but Red clover is considered their preferred source because it is the only plant containing all four major estrogenic compounds at very high levels [3].

Source

Red clover is a member of the family Leguminosae scientifically known as Trifolium pratense. It is one of the world’s oldest agricultural crops traditionally grown in Europe and the Far East, and more recently in America, as a medicinal herb for a variety of purposes and as a human food providing a source of protein.

It is a biennial or short-lived perennial plant that blooms in the summer with multiple, fragrant, red to purple flowers and leaves that consist of three oval-shaped leaflets with a distinctive, whitish, V-shaped marking. Linnea Red clover leaves, from which the extract is taken, are cultivated and harvested in respect of GAP (Good Agricultural Practices), ensuring full process traceability. The harvest–time coincides with the balsamic period of the plant and has been established over the years through close collaboration and partnerships between Linnea and each individual supplier.

Each batch coming from the plantations is identified by validated HPLC and TLC procedures that determine the total content of the ingredients and detect any contaminants present in accordance with the current standards.

Activity

Phenolic phytoestrogens have a chemical structure similar to that of steroidal estrogens, enabling them to interact directly with the human Estrogen Receptors (ER) present on all human cells. Isoflavones have both estrogenic and anti-estrogenic effects on metabolism according to their concentration, the levels of endogenous estrogens and individual characteristics, such as gender and menopausaI status.

The Biochanin and Formononetin estrogenic activity is in the order of 1’000 times less than that of 17ß-estradiol. However, when taken as supplement in the effective dosage, plasma levels of isoflavone active metabolites have a comparable estrogenic activity [1,4] conferring in addition the general benefits of the phytocomplex.

Biochanin A may also have a protective effect on blood vessels and the cardiovascular system, by inhibiting vascular remodelling and neointima formation. Like Genistein it has also been shown to induce endothelium-independent relaxation of coronary arteries. In addition Formononetin has been shown to significantly enhance osteoblast cell proliferation, stimulate alkaline phosphate production and protect cells against apoptosis [5].

Common Applications and Evidence

Hormone Replacement Therapy (HRT) in many women has proved effectiveness in reducing physical and emotional symptoms and helping to protect against heart disease and osteoporosis. However, many patient treated suffer unwanted side effects, such as bloating, irritability, and breast tenderness [6]. The North American Menopause Society (NAMS) initially recommends changes to lifestyle combined with an alternative treatment strategy for both symptom relief and disease prevention [8]. Red clover dietary isoflavones are the most appropriate first line treatment for moderately symptomatic women who are advised to undergo a 12 week treatment period together with changes in lifestyle. The non-hormonal prescription medication is also recommended for patients in whom HRT is contraindicated or who refuse such therapy. Considering the phytoestrogen-rich composition and the antioxidant activity of Red clover, the extract may also play a role in combating prostate cancer by reducing the proliferation of hormone dependent prostate cells and acting as an antioxidant and free radical scavenger [7].

Clinical evidence

A large number of studies have been conducted on over 1’000 women by specialists at universities and teaching hospitals under close ethical supervision, in accordance with the Good Clinical Research Practice guidelines.

Treatment of menopausal symptoms

Several trials, conducted for a minimum period of three months, showed a statistically significant reduction in several menopause symptoms assessed using the Kupperman index including hot flushes, night sweats, anxiety and depression [9].

Vasomotor Symptoms (Hot Flushes)

In two recent double blind placebo controlled studies, 80 mg of Linnea Red clover extract was administered for 12 and 16 weeks treatment to postmenopausal women. A statistically significant reduction (of about 45%) in both the frequency and severity of hot flashes was reported between the treated group and the placebo group [9,10].

Osteoporosis/Bone Health

The bone preserving properties of Red clover have been examined in several randomized, placebo-controlled trials, demonstrating a positive effect of Red clover on bone mineral density as well as an increase in bone formation markers. Moreover the loss of lumbar spine bone mineral content was significantly lower, suggesting a potentially protective effect [11].

Anxiety -Vaginal Atrophy -Mastalgia

Red clover derived isoflavones were found to be more effective than placebo in reducing depressive and anxiety symptoms among postmenopausal women with a 77% decrease in the total score on the Hospital Anxiety and Depression Scale (HADS) and an 81% decrease in the score on the Zung’s Self Rating Depression Scale (SDS) [12]. The administration of Red clover isoflavones has also been correlated with a significant decrease in mastalgia symptoms [13], endometrial thickness, uterine blood flow and an improvement in the vaginal maturation index [14].

Cardiovascular health

The vascular effects of Red clover as potential contributors to the cardio protective properties were studied in two 12 week, double-blind, randomised trials on postmenopausal women. In women with borderline hyperlipidaemia, a significant increase in high-density lipoprotein cholesterol and a reduction in apolipoprotein were observed from baseline to 12 weeks [15,16]. A 12 week, double-blind, randomised, dose-escalating study was conducted to investigate the effects of two dose levels of the Red clover formulation (40 mg and 80 mg) versus placebo on arterial compliance. The differences between Red clover and placebo were significant for both treated groups [17].

Prostate health

A study conducted at the Austria Landesklinikum Thermenregion Baden assess the effect of chronic isoflavone in male patients treated for 1 year with a daily intake of 60 mg of Red clover extract. The most important finding was a significant reduction in the Prostate-Specific Antigen (PSA) levels [18].

Technical Description
Name of the plant Red clover, Trifolium pratense
Part of the plant used Aerial parts of the plant
Chemical definition Mixture of isoflavones:
Biochanin A, Formononetin, Daidzein and Genistein
Synonyms Pavine clover, Cow grass

Structural Formula
red_clover

Bibliografic References
  1. A Review of the Clinical Effects of Phytoestrogens. Obstetrics And Gynecology 1996; 87{5 Pt 2):897-904. Knight DC and Eden JA.
  2. Japanese intake of flavonoids and isoflavonoids from foods. S. JEpidemiol 1998; 8(3):16875 Kimira M, Arai Y, Shimoi Kand Watanabe
  3. Phytoestrogens Content of Foods - G A Compendium of Literature Values. Nutr. Cancer 26 (2): 123-148, 1996. Reinli K, Block
  4. Phytoestrogens: a Review of the Present State of Research. Phytother. Res. 17, 845–869. 2003. Andreana L. Ososki and Edward J. Kennelly
  5. Growth inhibition of human endothelial cells by the phytooestrogen biochanin A, a metabolite of genistein. Br J Nutr. 2001 May;85(5):615-20. Ying C et Al.
  6. Isoflavones and Women’s Health. Breast Cancer Research 2004; 4(3):140-142 . Powles T.
  7. Estrogenic activity of two standardized Red clover extract (Menoflavon) intended for large scale use in hormone replacement therapy. Journal of Steroid Biochemistry & Molecular Biology 78-2001: 67-75. E. Dornstauder et Al.
  8. Treatment of menopause-associated vasomotor symptoms: position statement of The North American Menopause Society. North American Menopause Society. Menopause. 2004 Jan- Feb;11(1):11-33
  9. Isoflavones from Red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas 2002. Van de Weijer et al.
  10. The use of an Isoflavone supplement to relieve hot flushes. The Female Patient 2002. Jeri.
  11. The effects of phytoestrogen isoflavones on bone density in women: A double-blind, randomized, placebo-controlled trial. American Journal of Clinical Nutrition. 2004. Atkinson C, Compston JE, Day NE, Dowsett Mand Bingham SA.
  12. Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from Red clover extracts. Maturitas. 2010 Mar;65(3):258-61. Epub 2009 Nov 30. Lipovac M, Chedraui P, Gruenhut C, Gocan A, Stammler M, Imhof M.
  13. A double blind randomised controlled trial of isoflavones in the treatment of cyclical mastalgia. Breast 2002. lngram DM, Hickling C,West L, Mahe U and Dunbar PM.
  14. Effects of red dover isoflavones (Promensil) versus placebo on uterine endometrium, vaginal maturation index and the uterine artery in health postmenopausal women. Journal of the British Menopause Society 2003. Woods R, Colville N, Blazquez J, Cooper A, Whitehead MI.
  15. Effects of isoflavone phytoestrogens on lipid profile in postmenopausal Peruvian women. Abstract presented at the International Menopause Society Conference, Berlin 2002. Jeri A. Paper presented at: 9th International Menopause Society World Congress on the Menopause; October 20, 1999; Yokahama, Japan.
  16. Influence of Red clover-derived isoflavones on serum lipid profile in postmenopausal women.
  17. Terzic MM, Dotlic J, Maricic S, Mihailovic T, Tosic-Race B. J Obstet Gynaecol Res. 2009 Dec;35(6):1091-5.
  18. Isoflavones from Red clover improve systemic arterial compliance but not plasma lipids in menopausal women. Nestel PJ, Pomeroy S, Kay S, Komesaroff P, Behrsing J, Cameron JD, West L Journal of Clinical Endocrinology and Metabolism 1999
  19. Effects of One-Year Treatment with Isoflavone Extract from Red clover on Prostate, Liver Function, Sexual Function, and Quality of Life in Men with Elevated PSA Paul F. Engelhardt and Claus R. Riedl UROLOGY 71:185–190, 2008).

 

red clover