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Clinical studies of red clover (Trifolium pratense) dietary supplements in menopause: a literature review

Booth, Nancy L. PhD; Piersen, Colleen E. PhD, MBA; Banuvar, Suzanne MHSA, CCRC; Geller, Stacie E. PhD; Shulman, Lee P. MD, FACOG, FACMG; Farnsworth, Norman R. PhD

doi: 10.1097/01.gme.0000198297.40269.f7

Red clover (Trifolium pratense L., Fabaceae) botanical dietary supplements have received much attention recently for their potential use in the treatment of menopause symptoms, maintenance/improvement of bone and cardiovascular health, and reported benign effects on the breast and endometrium. Literature searches of four computerized databases were run to identify clinical studies of red clover botanical dietary supplements. The manufacturer of the red clover products used in the majority of the studies was contacted for unpublished information and/or clarification regarding the chemical content of their products. Red clover studies were reviewed that pertained to women‘s health or menopause. Clinical evidence is presently lacking to support the efficacy of semipurified red clover isoflavone extracts for alleviation of climacteric vasomotor symptoms or reduction of low-density lipoprotein levels in the blood. Furthermore, the safety of use of red clover isoflavone supplements in patients with breast or endometrial cancer has not been established. Limited evidence suggests possible efficacy in maintenance of bone health and improvement of arterial compliance, a risk factor for atherosclerosis. This literature review covers red clover botanical dietary supplement clinical studies having a possible impact on the health care of mature and menopausal women, and provides historical perspective regarding the traditional uses of red clover.

This literature review covers clinical studies of red clover pertaining to its use in women's health and menopause. Some traditional uses of red clover are included for perspective, and clinical studies are summarized under the headings of cognitive effects, bone health, cardiovascular health (including both vascular and lipid effects), breast effects, endometrial effects, insulin effects, and antioxidant effects.

From the 1UIC/NIH Center for Botanical Dietary Supplements Research, Program for Collaborative Research in the Pharmaceutical Sciences (PCRPS) and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL; 2Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL; and 3Department of Obstetrics and Gynecology, College of Medicine, University of Illinois at Chicago, Chicago, IL. N.L.B. is currently located at the Molecular Targets Development Program, Center for Cancer Research, NCI-Frederick, Frederick, MD.

Received April 13, 2005; revised and accepted June 16, 2005.

This work was supported, in part, by Grant P50 AT00155 provided jointly by the National Center for Complementary and Alternative Medicine (NCCAM), the Office of Dietary Supplements (ODS), the Office for Research on Women‘s Health (ORWH), and the National Institute of General Medicine (NIGMS) of the National Institutes of Health (NIH). N.L.B. is grateful for the receipt of NIH National Research Service Award F31 AT00804. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH funding agencies.

Address correspondence to: Norman R. Farnsworth, PhD, UIC/NIH Center for Botanical Dietary Supplements Research, and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., M/C 781, Chicago, IL 60612. E-mail:

© 2006 by The North American Menopause Society.