Red clover benefits and side effects
September 26, 2011
There are only a few studies about red clover benefits on high cholesterol, cancer and hot flush.

Red clover benefits - CHOLESTEROL-LOWERING PROPERTIES
Nestel P et al, Monash University, Australia, found that isoflavones from red clover enriched in biochanin (genistein
precursor) but not in formononetin (daidzein precursor), lowered LDL-C in men. And, this biochanin effect was
confined to men (male only). [3]

Campbell MJ, Royal Free and University College London Medical School, London, UK, found that 1-month
supplementation with red clover isoflavones(86 mg/day red clover-derived isoflavones) increased HDL in
postmenopausal women compared to placebo (P=0.02) but did not alter either cholesterol or triacylglycerol
concentrations, and had no effect on antioxidant status. [4]

Red clover benefits on HOT FLUSHES
van de Weijer PH and Barentsen R, Universiteit Medical Centre, The Netherlands, found that Isoflavones from red
clover (80 mg isoflavones , Promensil) significantly reduce menopausal hot flush symptoms compared with placebo in
their randomized, double blind, placebo-controlled trial. In this trial, 30 women with more than 12 months amenorrhoea
and experiencing more than five flushes per day were enrolled. [5]

Howes JB et al, St. George Hospital,  Australia, fed 30 postmenopausal women aged greater than 60 years with either
two tablets of an extract of aglycone isoflavones from red clover or placebo for 6 months in a randomized, controlled
clinical trial. They found  that isoflavone supplementation was associated with an apparent improvement in block
design (a test of visual-spatial intelligence), but no improvement in verbal memory and a deterioration in digit recall. [8]
In another study, Gordon A, Harrisburg Family Practice Residency, USA, also commented that both red clover extracts
and placebo equally reduce the frequency of hot flushes. [6]

While, Tice JA et al, University of California, San Francisco, commented that although their study provided some
evidence for a biological effect of Promensil, neither supplement had a clinically important effect on hot flashes or
other symptoms of menopause. Theirs was a randomized, double-blind, placebo-controlled trial of 252 menopausal
women, aged 45 to 60 years, who were experiencing at least 35 hot flashes per week. After a 2-week placebo run-in,
252 participants were randomly assigned to Promensil (82 mg of total isoflavones per day), Rimostil (57 mg of total
isoflavones per day), or an identical placebo, and followed-up for 12 weeks. [7]

The conflicting data about the benefits of red clover indicates the importance of the experimental and dosage form
designs. Probably, the nature (i.e. the conditions) of the subjects also contribute a part in the outcome of the studies.

Red clover benefits - ANTI-TUMOR PROPERTIES
A few studies show that red clover may benefit patients suffered from cancers.

[1] Cassady JM et al, Purdue University, Indiana, developed an assay to screen and fractionate plant extracts for
chemopreventive potential in 1988. This assay measures effects on the metabolism of [3H]benzo(a)pyrene [B(a)P] in
hamster embryo cell cultures. Screening of several plant extracts has generated a number of activity leads. They
found that biochanin A decreased the metabolism of B(a)P by 54% in comparison to control cultures and decreased
B(a)P-DNA binding by 37 to 50% at a dose of 25 micrograms/ml. They suggested that in vivo studies of this compound
as a potential chemopreventive agent are warranted  [9]

[2] Jarred RA et al, Monash Institute of Reproduction & Development, Monash University, Australia, recruited 38
patients diagnosed with prostate cancer into a study. They asked 20 men to consume 160 mg/day of red
clover-derived dietary isoflavones, containing a mixture of genistein, daidzein, formononetin, and biochanin A before
surgery. They followed up their serum PSA, testosterone, biochemical factors, clinical and pathological parameters.
They studied the incidence of apoptosis in prostate tumor cells from radical prostatectomy specimens from 18 treated
and 18 untreated control tissues. They found that the apoptosis in radical prostatectomy specimens from treated
patients was significantly higher than in control subjects. And, they did not find any side effects/adverse events. [10]

[3] Almost at the same time, Rice L et al, University of Florida, USA, used LNCaP cells and xenografts to investigate
the mechanisms of the antiproliferative effects of biochanin A, a major isoflavone present in red clover but not
soy-derived products. They exposed cells to varying doses of biochanin A to evaluate viability, DNA synthesis, and
DNA fragmentation (TUNEL) analysis. They found that biochanin A induced a dose-dependent inhibition of
proliferation and [(3)H]thymidine incorporation that correlated with increased DNA fragmentation, indicative of
apoptosis. Western blot analyses of cell cycle regulatory proteins revealed that biochanin A significantly decreased
expression of cyclin B and p21, whereas flow cytometry showed that cells were accumulating in the G(0)/G(1) phase.
Consequently, they concluded that biochanin A inhibited prostate cancer cell growth through induction of cell cycle
arrest and apoptosis. [11]
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Red Clover Side Effects
According to the website of University of Maryland (September 26, 2011), there is no serious red clover side effects for
short term use, while the general red clover side effects may include headache, nausea and rash. Overdose of red
clover in animals led to infertile. Further, NIH
website (September 26, 2011) states that "Because red clover contains
estrogen-like compounds, there is a possibility that its long-term use would increase the risk of women developing
cancer of the lining of the uterus
." Thus, the red clover side effects can be serious if it is for long term use or if the
users are overdosed.

People suffered from breast cancer, or other hormone-sensitive cancers should not take red clover. Red clover
increase resistance of prostate cancer cells to high dose radiation, in vitro. Patients should avoid use of red clover
during radiotherapy for prostate cancer. Further, Red clover may increase the effects of anticoagulants and
antiplatelet drugs. [
Website of Memorial Sloan-Kettering Cancer Center, September 26, 2011]
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Reference:
[1] Health and Age, on-line publication, January 2005 [2] J Br Menopause Soc. 2004 Mar;10 Suppl 1:7-12]. [3] [Eur J Clin Nutr. 2004
Mar;58(3):403-8][4 ] [Eur J Clin Nutr. 2004 Jan;58(1):173-9][5]  [Maturitas. 2002 Jul 25;42(3):187-93] [6]  [J Fam Pract. 2003
Nov;52(11):846-7]. [7]  [JAMA. 2003 Jul 9;290(2):207-14] [8] Climacteric. 2004 Mar;7(1):70-7.][9][Cancer Res. 1988 Nov
15;48(22):6257-61 [10] Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1689-96] [11][Prostate. 2002 Aug 1;52(3):201-12]
Red clover is a perennial herb that can be found in Europe and Asia, and has now been naturalized to grow in North
America. The ends of the branched stems may benefit on various conditions. Red clover is marketed as red clover
tea, red clover pills (supplements).
Red Clover Benefits
Red clover is a rich source of calcium, chromium, magnesium, niacin, phosphorus, potassium, thiamine, vitamin C as
well as isoflavones [1] Isoflavones are water-soluble chemicals that act like estrogens and are found in many plants.
Isoflavones may significantly reduce hot flashes in menopausal women. [2]

Traditionally, red clover has been used for cancer and respiratory problems, such as whooping cough, asthma, and
bronchitis. Current uses of red clover are for menopausal symptoms, breast pain associated with menstrual cycles,
high cholesterol, osteoporosis, and symptoms of prostate enlargement. [
NIH publication] While, according to the
website of Memorial Sloan-Kettering Cancer Center (September 26, 2011), the purported uses of red clover are chest
congestion, menopausal symptoms and spasm.
side effects and benefits of a product. You are encouraged to report adverse side effects to FDA, its website is www.fda.gov., or report the adverse
side effects to the manufacturer, you should be able to find the contact information on the label.

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