Red clover, isoflavones

Black cohosh may cause nausea, vomiting, hypotension, and even miscarriage. It is absolutely contraindicated in pregnancy. Red clover contains coumarins and should therefore be avoided with anticoagulants. Diets high in red clover isoflavones have reduced livestock fertility and theoretically could do the same in humans. Flaxseed may cause nausea, diarrhea, and flatulence. Cyanogenic nitrates in flax (especially in immature seed pods) have produced toxic reactions. 

In a meta-analysis of clinical trials of monopreparations containing red clover isoflavones, the reviewers noted that there was no apparent evidence of adverse events during short-term use of red clover, but long-term studies were... 

Red clover contains isoflavones, compounds that are structurally similar to the human hormone estradiol and capable of binding to estrogen receptors (Umland et al. 2000). Some studies have indicated that red clover isoflavones have a greater affinity for the estrogen receptor P (found primarily in bone, brain, heart, and vascular system) than estrogen receptor a (found primarily in uterus, breast, ovaries, and adrenal glands) (Beck et al. 2005 Dornstauder et al. 2001). 

A second meta-analysis, including six placebo-con-trolled red clover isoflavone trials, with doses ranging from 40 to 80 mg daily, and study duration from 12 to 16 weeks, concluded that adverse events did not differ between isoflavone and placebo groups, although the events were not well characterized in several trials. Gastrointestinal symptoms were generally the most common adverse events in both isoflavone and placebo groups (Nelson et al. 2006). 

In women aged 35 to 70 with at least one first-degree relative with breast cancer, administration of 40 mg of red clover isoflavones daily for 3 years did not result in any significant differences in breast density, endometrial thickness, serum cholesterol, follicle-stimulating hormone levels, or bone mineral density, as compared to placebo. In postmenopausal women, some differences in bone marker levels were seen between active and placebo groups at 6 and 12 months (Powles et al. 2008). 

An extract of a red clover isoflavone preparation increased MCF-7 breast cancer cell proliferation rates (Bodinet and Freudenstein 2004). A standardized red clover isoflavone extract (9% isoflavones by dry weight) showed an affinity for both estrogen receptor (ER) a and P with a significantly stronger affinity for the ERP receptor in a yeast two-plasmid system (Dornstauder et al. 2001). 

An ethanolic extract of a commercial red clover preparation inhibited the drug-metabolizing isoenzyme CYP3A4 in a fluorometric microtiter plate assay (Budzinski et al. 2000). Genistein and daidzein, metabolites of the predominant red clover isoflavones biochanin A and formononetin, were shown to inhibit the enzyme CYPIBI (Roberts et al. 2004). 

Hale, G.E., C.L. Hughes, S.J. Robboy, S.K. Agarwal, and M. Bievre. 2001. A double-blind randomized study on the effects of red clover isoflavones on the endometrium. Menopause 8(5) 338-346. 

Hidalgo, L.A., P.A. Chedraui, N. Morocho, S. Ross, and G. San Miguel. 2005. The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women A randomized, double-bUnd, placebo-controlled study. Gynecol. Endocrinol. 21(5) 257-264. 

Powles, T.J., A. Howell, D.G. Evans, et al. 2008. Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Menopause Int. 14(1) 6-12. 

Lam ANC, Demasi M, James MJ, Husband AJ, Walker C (2004) Effect of red clover isoflavones on cox-2 activity in murine and human monocyte/macrophage cells. NutrCtmcer49(l) 89-93... 

Based on these facts, in 2008, a group of Department of Biotechnology, University of Natural Resources and Applied Life Sciences Vienna, Vienna, Austria examined the possibility of biochanin A (pratensol, 41) and formononetin (biochanin B, pratol, 42) (Figure 10) as their ligands against the hiunan aryl hydrocarbon receptor. Then, for the purpose, it was tested whether or not biochanin A (pratensol, 41) and formononetin (biochanin B, pratol, 42) of two red clover isoflavones in the prescription for the improvement of the menopausal eomplaints could transactivate the aryl hydrocarbon receptor (AhR). 

Trifolium pratense (red clover)" Isoflavones Women s health, e.g., hot flushes... 

Sivesind, E. Seguin, R (2005). Effects of the environment, cultivar, maturity, and preservation method on red clover isoflavone concentration. Journal of Agricultural and Food Chemistry, 53,6397-6402. 

TSUNODA N, POMEROY s, NESTED p (2002) Absorption in hiunans of isoflavones from soy and red clover is similar. JNutr 132, 2199-2201. 

Several studies have evaluated dietary supplements such as isoflavones, which are found in soy products and red clover. A well-controlled trial in more than 400 postmenopausal women evaluating a specific isoflavone, ipriflavone, found no benefits on bone mineral density or fracture rates after 3 years.47 Nevertheless, because these therapies are available without prescription and are not regulated by the FDA, patients may choose to self-medicate with isoflavones. Lymphocytopenia appeared in several patients treated with ipriflavone in clinical trials. Additionally, ipriflavone should be used with caution in immunocompromised patients or those with renal disease. It may inhibit CYP1A2 and CYP2C9 and may interact with drugs metabolized by those pathways, such as warfarin. 

Klejdus B, Vitamvasova D and Kuban V. 2001. Identification of isoflavone conjugates in red clover (Trifolium pratense) by liquid chromatography-mass spectrometry after two-dimensional solid-phase extraction. Anal Chim Acta 450 81-97. 

Phytoestrogens are a diverse group of polyphenolic non-steroidal plant compounds that bind to human estrogen receptors (Cos et al., 2003). The best studied of these compounds are the isoflavones, the phytoestrogens present in soy and red clover. 

Red clover is a plant that contains isoflavones in a slightly different composition compared with soy. Red clover contains formononetin and biochanin A, which are not present in soy and may thus have additional biological activity. So far, four studies (Barber et ah, 1999 Knight et ah, 1999 van de Weijer, 2002 Tice et ah, 2003) have been performed using isoflavones derived from red clover (Table 4.3). These have used doses of isoflavones ranging from 40 to 160 mg. Three out of four of these studies did not show any effects, even in spite of a very large sample size (Tice et ah, 2003). Only one study showed a reduction in the number of hot flushes. The reduction, however, was small (van de Weijer and Barentsen, 2002). Red clover therefore does not appear to have much of an effect on the reduction of hot flushes. 

Effects of isolated isoflavones derived from red clover. 

Clifton-Bligh, P.B., Barber, R.J., Fulcher, G.R., Nery, M.L. and Moreton, T. (2001). The effect of isoflavones extracted from red clover (rimostril) on lipid and bone metabolism. Menopause, 8, 259-265. 

Howes, J.B., Sullivan, D., Lai, N., Nestel, P., Pomeroy, S., West, L., Eden, J.A. and Howes, L.G. (2000). The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate h5q)ercholesterolaemia, Atherosclerosis, 152, 143-147. 

Nestel, P.J., Pomeroy, S., Kay, S., Komesaroff, P., Behrsing, J., Cameron, J.D. and West, L. (1999). Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women, J. Clin. Endocrinol. Metab., 84, 895-898. 

Five out of 18 products containing soy or red clover were found to have as little as half the amount of isoflavone, the natural product they were designed to deliver, claimed on the label. 

Isoflavones, chiefly found in the Leguininosae (such as soy, Medicago sativa, and red clover. Trifolium pratense) in the plant kingdom, are also successfully analyzed by HPLC on Ci8 columns. ... 

Atkinson C, Warren RML, Sala E et al. Red clover-derived isoflavones and mammographic breast density a double-blind, randomized, placebo-controlled trial. Breast Cancer Res. 6, R170-R179, 2004. 

Atkinson C, Oosthuizen W, Scollen et al. Modest protective effects of isoflavones from a red clover-derived dietary supplement on cardiovascular disease risk factors in perimenopausal women, and evidence of an interaction with ApoE genotype in 49-65 year-old women. J. Nutr. 134, 1759-1764, 2004. 

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