Red Clover

Latin name: Trifolium pratense L. [Fabaceae]
Plant part: Leaf

Red clover is a member of the pea family, and is an extensive agricultural
crop. The leaves and flowers contain a class of compounds
called isoflavones that includes formononetin, daidzein, and genistein.
Red clover products are characterized and standardized according
to the quantity and composition of these isoflavones (Kelly, Husband,
and Waring, 1998).

Clinical studies have been conducted with a standardized extract
of red clover leaves. This extract is incorporated into tablets called
Promensil™, manufactured by Novogen Laboratories Pty Ltd.,
NSW, Australia, and distributed in the United States by Novogen
Inc., Stamford, Connecticut. The tablets are characterized as containing
40 mg isoflavones, including biochanin (24.5 mg), formononetin
(8.0 mg), genistein (4 mg), and daidzein (3.5 mg). One of the studies
(Samman, 1999) used an unnamed Novogen product with a very similar
composition. The tablets contained 43 mg isoflavones, consisting
of biochanin A (25.7 mg), formononectin (9.3 mg), genistein (4.3
mg), and daidzein (3.7 mg).


Some plants in the pea family, including red clover and soy, contain
isoflavones that have weak estrogenic activity. With the waning
of estrogen levels in menopause, these phytoestrogens are thought to
help compensate and thus reduce the symptoms that may include hot
flashes, sweating, cardiovascular complaints, fatigue, vertigo, muscle
 and joint pain, urinary incontinence, vaginal dryness, and atrophy
of the vaginal epithelium. Other symptoms of a psychological nature
may include irritability, forgetfulness, anxiety, depression, sleep disturbances,
and reduced libido. Menopausal symptoms occur when a
woman’s ovaries no longer contain eggs. The resulting decline in
ovarian function causes a reduced production of estrogen and progesterone,
and a corresponding increase in follicle stimulating hormone
(FSH) and luteinizing hormone (LH) (Murray and Pizzorno, 1999).

An Asian diet is estimated to deliver 25 to 45 mg total isoflavones
per day, whereas the Western diet is estimated to contain less than 5
mg. Epidemiological data imply that the lower incidence of menopausal
symptoms in Japanese women compared withWestern women
may be related to an enhanced dietary intake of soy isoflavones. A soybased
diet is also thought to explain the relatively low incidence of cardiovascular
disease in Southeast Asia, since the diet is correlated with
low levels of plasma cholesterol (Glazier and Bowman, 2001; Barnes,
1998).

 Menopausal Symptoms

The first menopausal study was a well-designed, three-month trial
including 35 women (40 to 65 years of age) with at least three hot
flashes a day, who were distributed into three groups: placebo; 40 mg
red clover extract (one tablet Promensil); and 160 mg red clover extract
(four tablets Promensil). No significant difference was observed
in the incidence of flashes between the three groups after three
months. Therewas also no difference in vaginal pH or serum levels of
FSH or sex hormone binding globulin (SHBG), a hormone-binding
protein (Knight, Howes, and Eden, 1999). Our reviewer, Dr. Tieraona
Low Dog, noted that the control group had increased urinary isoflavone
levels, indicating an inadvertent intake of dietary isoflavones
that would be a major flaw for the study.

The second study was a relatively good, randomized, double-blind
crossover study that enrolled 51 women with more than three hot
flashes a day. Subjects were given either one tablet Promensil daily or
placebo for three months, with the two treatment phases separated by
a month’s washout period. No significant difference was observed
between groups in reduction of hot flashes, levels of SHBG, vaginal
swab, or ultrasound examinations (Baber et al., 1999). Again the
study lacked control of dietary sources of isoflavones.