Trifolium pratense L.: an alternative for the treatment of vasoactive symptoms in pre and postmenopausal women
DOI:
https://doi.org/10.33448/rsd-v11i12.34695Keywords:
Red clover; Clinical trial; Hot flashes.Abstract
Menopausal women experience estrogen deficiency during this period, which causes vasomotor symptoms such as mood swings, hot flushes, palpitations, headache, irritation, and depression. There are several pharmacological treatments as well as the use of dietary supplements to control these clinical manifestations, however therapies from medicinal plants have been highlighted, among them Trifolium pratense L. Popularly known as Red clover, it has a record in the Therapeutic Memento and in the Anvisa's Herbal Medicines Form, being considered a therapeutic adjunct in the treatment of climacteric. An integrative and narrative review using the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index for Nursing and Allied Health Literature (CINAHL; www.ebscohost.com/cinahl/), Embase, PubMed, LILACS, MEDLINE, PsycINFO and Web of Science as keywords adopted: “Trifolium pratense”, “clinical trial” and “hot flashes”. As a complement to the review, protocols for studies and ongoing trials were searched on CriticalTrials.gov. What resulted after analysis of the articles, 7 records. It is noted that the plant species studied exhibits a wealth of isoflavones in its composition, these metabolites are considered selective modulators of estrogen receptors, and can act as agonist and antagonist of estrogen receptors. Significant results were observed with Trifolium pratense in relieving hot flashes in women, however further trials are needed to safely define this clinical practice.
References
Agência Nacional de Vigilância Sanitária (ANVISA) (2021). Formulário de Fitoterápicos. (2ª ed.). Farmacopeia Brasileira.
Alder, E. (1998). The Blatt-Kupperman menopausal index: A critique. Maturitas.
Augoulea A, Moros M, Lykeridou A, Kaparos G, Lyberi R, & Panoulis K. (2019). Psychosomatic and vasomotor symptom changes during transition to menopause. Przeglad Menopauzalny.
Barnes et al. (2000). Estrogen Receptor Binding Is Only Part of the Isoflavone Story, The Journal of Nutrition, 130(3),656S–657S, https://doi.org/10.1093/jn/130.3.656S.
Bennetts, H. W. et al (1946). A specific breeding problem of sheep on subterranean clover pastures in western Australia. Aust Vet J.
Brasil. Protocolos da atenção básica, (2016). Ministério da Saúde. Saúde das mulheres Instituto Sírio Libanês de ensino e pesquisa. Brasília, DF.
Brasil. Resolução RDC nº 26, de 13 de maio de 2014. (2014). Dispõe sobre registro de medicamentos fitoterápicos e o registro e a notificação de produtos tradicionais fitoterápicos. Órgão emissor: ANVISA - Agência Nacional de Vigilância Sanitária.
Chen, L-R, Ko, N-Y, & Chen, K-H (2019). Suplementos de Isoflavona para Mulheres na Menopausa: Uma Revisão Sistemática. Nutrientes, 11(11):2649. https://doi.org/10.3390/nu11112649.
Chen, Y. M. (2021). Red Clover Isoflavones Influence Estradiol Concentration, Exercise Performance, and Gut Microbiota in Female Mice. Front Nutr.
Coon, J. T. & Ernst, E. (2007). Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis. Phytomedicine, 14(2-3):153-9.
Cota, A. M. M. et al (2004). Fitoestrogênios: Valor terapêutico no climatério Phytoestrogens: Therapeutic Value In Climacteric. Rev Med Minas Gerais 14(4):262-6.
Crawford, S. L. et al (2013). Impact of dose, frequency of administration, and equol production on efficacy of isoflavones for menopausal hot flashes: A pilot randomized trial. Menopause, 20:936-945.
Crossetti, M. G .O., (2012). Revisão integrativa de pesquisa na enfermagem o rigor científico que lhe é exigido [editorial]. Rev Gaúcha Enferm. 33(2):8-9.
Davis, S. R. (2019). The Kupperman Index undressed. Maturitas.
Dietz, B. M. et al. (2016). Botanicals and their bioactive phytochemicals for women’s health. Pharmacological Reviews.
Ellison N. W., Liston A, Steiner J J, Williams W. M., & Taylor N. L.(2006). Molecular phylogenetics of the clover genus (Trifolium-Leguminosae). Mol Phylogenet Evol.
Freedman, R. R. (2014). Postmenopausal Physiological Changes. Curr Top Behav Neurosci.
Geller, S.E. et al. (2009). Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: A randomized controlled trial. Menopause.
Ghazanfarpour, M. et al (2016). Trevo vermelho para tratamento de ondas de calor e sintomas da menopausa: Revisão sistemática e meta-análise, Journal of Obstetrics and Gynaecology, 36:3, 301-311, Doi: 10.3109/01443615.2015.1049249.
Giorno, C. Del. et al. (2010). Efeitos do Trifolium pratense nos sintomas climatéricos e sexuais na pós-menopausa. Rev Assoc Med Bras.
Gupta M, Sharma V, Singh S K, Chahota R K, & Sharma T R (2017). Analysis of genetic diversity and structure in a genebank collection of red clover (Trifolium pratense L.) using SSR markers.Plant Genet Resour Characterisation Util.
Jenks, B.H. et al (2012). A pilot study on the effects of S-equol compared to soy isoflavones on menopausal hot flash frequency. J Womens Health (Larchmt), Jun,21(6):674-82. 10.1089/jwh.2011.3153.
Jou, H. J. et al (2008). Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones. Int J Gynaecol Obstet, 102:44-49.
Kanadys, W. et al. (2020). Efeitos do trevo vermelho (Trifolium pratense)isoflavonas no perfil lipídico das mulheres perimenopausal e pós-menopausa - Uma revisão sistemática e meta-análise. Maturitas, 132, 7-16.
Khan, S.W, & Khatoon, S.(2008). Ethnobotanical studies on some useful herbs of haramosh and Bugrote Valleys in Gilgit, Northern Areas of Pakistan. Pakistan J Bot.
Lambert, M. N. T. et al. (2017). Combined Red Clover isoflavones and probiotics potently reduce menopausal vasomotor symptoms. PLoS One.
Lipovac, M. et al (2012). The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women. Gynecol Endocrinol.
Liu, J. et al(2001). Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem. May,49(5):2472-9. doi: 10.1021/jf0014157. PMID: 11368622.
Maki, P.M. et al. (2009). Effects of botanicals and combined hormone therapy on cognition in postmenopausal women. Menopause.
Manica, et al. (2019). Efeitos das terapias na menopausa: uma revisão narrativa da literatura. J. Health Biol Sci., 7(1):82-88 doi:10.12662/2317-3076jhbs.v7i1.2064.p82-88.2019.
McCormick, C. A., Brennan, A., & Hickey, M. (2020). Managing vasomotor symptoms effectively without hormones. Climacteric.
Mendes, K. D. S., Silveira, R.C.C.P., & Galvão, C.M. (2008). Revisão integrativa: método de pesquisa para a incorporação de evidências na saúde e na enfermagem. Texto Contexto Enferm. 17(4):758-64.
Mustafa, et al (2021). Menopausa precoce no Brasil: uma revisão bibliográfica integrativa. Research, Society and Development, 10(14), e461101422323.
Mustafa, B. et al. (2012) Medical ethnobotany of the Albanian Alps in Kosovo. J Ethnobiol Ethnomed.
Nachtigall, L. E. (2001). Isoflavones in the management of menopause. J British Menopause Society,S1, 8-11.
Naftolin, F., & Stanbury, M. G. (2002). Phytoestrogens: are they really estrogen mimics? Fertility and Sterility, 77, 15-7.
Nestel, P. J. et al (1999). Isoflavones from red clover improves systemic arterial complianc but not plasm lipids in meno pausal women. J. Clin Endocrinol metab, 84: 895-898.
Piersen, C. E. et al (2004). Chemical and biological characterization and clinical evaluation of botanical dietary suplemente: a phase 1 red clover extract as a model. Curr. Med. Chem., 11, 1361-1374.
Ramos, G. P. et al (2012). Genetic variability of isoflavones in the USDA red clover core collection. Rev. Bras. Farmacogn. 22, 1241-1252.
Reed, S. D. et al (2013). Self-reported menopausal symptoms in a racially diverse population and soy food consumption. Maturitas, 75, 152-158.
Rosário, C. S. D. (2021). Mulher no climatério: sintomatologia, estilo de vida, alimentos funcionais e libido.
Rotem, C. (2007). Phito-Female Complex for the relief of hot flushes, night sweats and quality of sleep: Randomized, controlled, double-blind pilot study. Gynecol Endocrinol.
Russell, L. et al (2002). Phytoestrogens: A viable option? Am. J. Med. Sci. 324, 185–188.
Saad, G. A. et al. (2018) Fitoterapia contemporânea: tradição e ciência na prática clínica. (2ª ed.). Guanabara Koogan.
Sabudak, T. et al (2008). Antiinflammatory and antioxidant activities of Trifolium resupinatum var. microcephalum extracts. Asian J Chem.
Sabudak, T, & Guler, N. (2009). Review article Trifolium L. A review on its phytochemical and pharmacological profile. Phytotherapy Research.
Schmidt, P. J. et al. (2021). The short-term effects of estradiol, raloxifene, and a phytoestrogen in women with perimenopausal depression. Menopause. Jan 15,28(4):369-383. doi: 10.1097/GME.0000000000001724. PMID: 33470755, PMCID: PMC9022873.
Sousa, R.L. et al. (2000). Fidedignidade do Teste-reteste na Aplicação do Índice Menopausal de Blatt e Kupperman. Rev Bras Ginecol e Obs.
Takahashi, T. A., & Johnson K. M. (2015). Menopause. Medical Clinics of North America..
Tice, J.A. et al (2003). Phytoestrogen Supplements for the Treatment of Hot Flashes: The Isoflavone Clover Extract (ICE) Study: A Randomized Controlled Trial. J Am Med Assoc.
Utain, W. H. et al. (2015). S-equol: a potential nonhormonal agent for menopause-related symptom relief. J Womens Health (Larchmt), 24(3):200-8.
Vasiljevic S, Cupina B, Krstic D, Pataki I, Katanski S, & Milosevic B.(2011) Seasonal changes of proteins, structural carbohydrates, fats and minerals in herbage dry matter of red clover (Trifolium pratense L.). Biotechnol Anim Husb.,
Wang, X., & Dong K. (2021). Effect of formononetin from Trifolium pratense L. on oxidative stress, energy metabolism and inflammatory response after cerebral ischemia-reperfusion injury in mice. Food Science and Technology.
World Health Organization. WHO (2009). monographs on selected medicinal plants. Geneva, Switzerland: World Health Organization, 4:335-352.
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Copyright (c) 2022 Anna Cyntia Brandão Nascimento Maniçoba; Valéria Maria Sousa Leitão; Maria Beatriz Coutinho Moraes; Ana Paula Muniz Serejo; Tassio Rômulo Silva Araújo Luz; Flavia Maria Mendonça do Amaral; Denise Fernandes Coutinho
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