CHEMICAL COMPOSITION
Contains the isoflavones biochanin A, formo-
nonetin, genistein, and daidzein as major iso-
flavone constituents, in addition to pratensein,
pseudobaptigenin, glycitein, calycosin,
prunetin,^1 and trifoside (5-hydroxy-7-meth-
oxy-isoflavone-4^0 - O-b-D-glucopyranoside);
flavones (e.g., pectolinarin); coumarins (cou-
marin, medicagol, and coumestrol, etc.),2–5
with the presence of coumestrol disputed
(JIANGSU).^6 Other constituents include procya-
nidin polymers,^7 isorhamnetin glucosides,
trans- andcis-clovamide (L-dopa conjugated
withtrans- and cis-caffeic acids); trifoliin
(isoquercitrin); phaselic acid; a galactogluco-
mannan composed of a backbone of
b-(1!4)-linked D-glucose andD-mannose
units witha-(1!6)-linkedD-galactose side
chains; sugars; protein; a volatile oil contain-
ing furfural; resins, fat, and minerals (particu-
larly rich in magnesium, copper, and calcium);
phosphorus, vitamins, and others (DUKE 1 ;
JIANGSU; KARRER).8–11 Red clover produces
phytoalexins (pterocarpan types) in response
to viral or fungal infections.5,12–14
Some commercial solid extracts of red
clover have been reported to contain traces
of cannabinol, caffeine, scopolamine, isocou-
marin, phenylpentadienal, phenylhexadiene,
and nepetalactone (seealfalfa).^15 Contents of
the major isoflavone constituents show wide
variability.^16
PHARMACOLOGY AND BIOLOGICAL
ACTIVITIES
Topical application of genistein to the skin
of hairless mice after they were exposed to
ultraviolet radiation ameliorated the inflam-
matory edema reaction.^17 A red clover isofla-
vone-rich diet in mice with enlarged prostate
glands reduced the enlargement and serum
androgen levels.^18
Red clover has shown estrogenic properties
in animals that are due to its isoflavones (see
alfalfa).2,5,19–23Oral administration of a red
clover tops extract (standardized to contain
15% isoflavones) showed evidence of weak
estrogenic activity in ovariectomized rats.^24
In vitrotransactivation of human estrogen
receptorsaandbwas greater from biochanin
A, followed by daidzein, formononetin, and
genistein. However, the orders of potency
were 2–5 orders lower than that of 17b-estra-
diol. Biochanin A also exhibited a higher
affinity to progesterone and to androgen re-
ceptorin vitroand was followed in potency
by genistein, daidzein, and formononetin.^16
Oral administration of a red clover tops extract
(standardized to contain 15% isoflavones)
showed evidence of weak estrogenic activity
in ovariectomized rats.^24 In vitro, biochanin A
inhibited DNA damage in human mammary
gland cells exposed to a polycyclic aromatic
hydrocarbon carcinogen (DMBA).^25
In a randomized, double-blind, placebo-
controlled (RDPC) crossover trial, a biocha-
nin-rich extract of red clover (but not a
formononetin-rich extract) significantly low-
ered LDL cholesterol in men, whereas neither
extract was effective in postmenopausal wom-
en, nor had any effect on levels of HDL-c or
triglycerides in the men or women.^26 In pre-
menopausal women, a RDPC parallel study
found that subjects taking an isoflavone-rich
extract of red clover showed no significant
change in cholesterol, triaglycerol,lipoprotein
(a), insulin, or glucose levels.^27 Double-blind,
placebo-controlled trials have found that red
clover extracts caused HDL-cholesterol levels
to significantly increase in postmenopausal
women.28,29 Although they have failed to
effect serum total cholesterol, LDL-c, or tri-
glycerides, bone mineral density (BMD) was
significantly increased.28,30A RDPC in post-
menopausal women who experienced at least
five hot flushes/day found that daily supple-
mentation with an isoflavone-rich extract of
red clover (standardized to contain largely
biochanin A and formononetin) reduced
both the severity and the frequency of hot
flushes.^31 However, a study of the same length
and design using the same extract and
dosage failed to find a significant reductionClover tops, red 207