Isoflavones toxicity

Sesamex [51-14-9] (Sesoxane) (30) is a synergist oflow toxicity, acute oral LD q (rat) = 2000 2270 mg/kg, for pyrethrins and allethrin. 6,7-Dihydroxy 4-methylcoumarin has been offered as an antioxidant for phenoHcs and polymers, and as an anthelmintic. 2,4,5-Trihydroxybutyrophenone has been available as an antioxidant and light stabilizer for polyolefins, waxes, and foods. Isoflavones, eg (31), have been patented as components of antioxidant compositions for foods and cosmetics (qv) (97). 

In a 1996 review, the Committee of Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) estimated the intake of isoflavones from soya-milk to be approximately 4 mg/kg/day over the first 4 months of life. This is greater than that associated with hormonal effects in premenopausal women, but the COT nonetheless supported the existing Department of Health s advice that... 

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. 

Although toxicity from isoflavones may arise from their action as alternative substrates for the enzyme thyroid peroxidase and people in southeast Asia would be protected by the dietary inclusion of iodine-rich seaweed products, a recent study has shown that isoflavone supplements do not affect thyroid function in iodine-replete postmenopausal women. Considerations of the safety of soy isoflavones is an area of great interest in relation to their potential benefits to human health and has recently been comprehensively reviewed. ... 

To test the validity of the bioassay itself we prepared a diet containing increasing amounts of rotenone, a compound derived from isoflavones and thus chemically not far removed from the soybean phytoalexins. Results in this case followed exactly the expected dose response curve (Table VII). Both survival and weight gain of larvae were drastically affected by increasing concentrations of rotenone. This experiment showed that the bioassay would be capable of detecting toxic effects of the phytoalexins on the soybean looper larvae, if such effects were acute. It showed also that the detoxification mechanisms in the soybean looper, a rather polyphagous insect, may permit it to adequately overcome the antibiotic effect of the isoflavonoid phytoalexins, but not that of the isoflavone rotenone. 

The flavonoids, derivatives of flavone (353) and of isoflavone (354), are widely distributed among plants of many kinds. They provide colour (from pale yellow to orange) in flowers and their potential as dyes is being revived now that awareness of the toxicity of some synthetic dyes is increasing, for example morin (355 CI. Natural Red) is one of many... 

Gutierrez-Zepeda A, Santell R, Wu Z, Brown M, Wu Y, Khan I, Link CD, Zhao B, Luo Y. 2005. Soy isoflavone glycitein protects against beta amyloid-induced toxicity and oxidative stress in transgenic Caenorhabditis elegans. BMC Neurosci 6 54. 

Once the benefits of a key component in food are documented, the challenge is to increase its concentration, and presumably its benefits, while maintaining safety. For example, isoflavones in soy are phytoestrogens with a chemical structure similar to estrogen. Isoflavones may reduce cholesterol, but what is the risk of increasing the intake of a compound that may modulate estrogens Knowledge of the toxicity of functional food components is crucial to improve their benefit-risk ratio. The efforts... 

Genistein and daidzein directly affect testosterone metabolism, reducing the toxic metabolites of testosterone. Genistein, an isoflavone, also seems to slow or prevent the metastasis of invasive cancer cells. It is believed to work by preventing the formation of new blood vessels to cancerous tumors. Histoculture studies of genistein have shown that this phytochemical reduces the growth of prostatic cancer tissue. 

The R. are generally toxic. They are soluble in organic solvents. Chemically the C20 or C23 compounds are chromanofiirochromones (see furocoumarins) or, respectively dichromanopyrones which can be considered as being derived tom the isoflavones for biosynthesis, see Lit.. The activity as an insecticide is based on an impairment of electron transport in the mitochondria caused by an inhibition of the citric acid cycle. 

The isoflavones luteone (86) and wighteone (87) occur on the leaf surfaces of Lupinus species and appear to be preformed antifungal defenses both compounds are fungi-toxic to Helminthosporium carbonum (Harbome, 1986, 1991). 

To conclude on the last two sections on health effects, one can say that polyphenols are generally regarded as safe and there are only a few reports on possible toxic effects (yet not in the case of isoflavones and lignans in humans) [214—217]. However, polyphenols have the potential to interact with sensitive hormonal systems. Moreover, as impUed above when discussing bioavailabflity, efficient cmiJugatirHi and excretion mechanisms as well as relatively low phenolic crmcentratirHis in blood... 

A few examples are found of the toxicity of some of the phenolics to livestock. The phenol ether, tremetone, from Eupatorium rugosum, caused toxic effects in livestock as did the isoflavones, genistein, and coumestrol (93). 

Isoflavones have been found in higher concentrations only in the legume family of plants (Fabaceae) and occur in significant amounts only in soybeans and soya bean products. Isoflavones exhibit oestrogenic activity, but also further toxic effects, and are often classified, together with other active compounds, as phytoestrogens (see Section 10.4). 

A number of isoflavones exhibit, in addition to oestrogenic activity, antimicrobial activity and other toxic effects. Examples of isoflavones exhibiting antimicrobial properties are prenylated isoflavones of legumes listed in Section 10.3.3.5.1, which occur mainly on the surface of leaves and other aboveground plant parts. Examples of such compounds are wighteon and luteon, which occur in lupines Lupinus spp.) together with other related compounds. 

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