# Improved Food-Processing Techniques to Reduce Isoflavones in Soy-Based Foodstuffs
## 1 Introduction  
Isoflavones (IFs) are polyphenols bearing both estrogenic and antiestrogenic traits, among other properties. It has been shown that they exhibit beneficial health effects, especially in people with an oestrogen deficiency, i.e., women in natural or artificial menopause [1, 2]. Indeed, IFs at doses of 40 mg/day or more could prevent vasomotor symptoms associated with menopause. Some other meta-analysis suggested that phytoestrogens from soy could prevent bone loss in menopause via an estrogenic effect [3, 4, 5], and even more efficiently under aglycone forms [6]. However, alongside these potential beneficial effects, menstrual cycle impairments were observed in women exposed to IFs in doses of about 0.75 mg/kg bw (body weight)/day in aglycone forms [7, 8]. More recently, IF intake at a level of 50 mg/day in women, i.e.,about 0.8 mg/kg bw/day, was shown to be significantly correlated with luteal phase impairment and with the risk of nulliparity at 26 years old [9; 10]. In addition, five clinical or population studies have so far reported the association of high soy IFs intake and their biomarkers in body fluids with a reduction in sperm count and quality [11; 12; 13; 14; 15]. When studies reported no effects on semen quality in men, it was at low doses [16] or for too short exposure times [17]. Overconsumption of soy has also been linked to several adverse clinical cases in women [18] and men [19]. In the former, on one hand, menstrual cycles were impaired and contraceptive pill treatments suffered from interference, and on the other hand, large uterus fibrosis and endometriosis features were observed. The effects regressed after soy arrest. In men, a secondary hypogonadism, which is the impairment of sexual behaviour and the feature of gynecomastia, was observed. The hypogonadism, characterised by dramatically reduced sex steroid concentrations in the blood, tended to return to normal levels after 3 months without soy. IFs have also been the centre of a great controversy regarding breast cancer, with several studies concluding in favour of a protective effect, mainly in Asian populations [20], while others reporting a proliferative impact [21]. It is though currently admitted, thanks to a better understanding of their mechanisms of action, that IFs have a dual effect: protective during the promotion phase (healthy cells), but proliferative on already declared oestrogen-dependent cancer cells. For instance, the activation of GPER, inducing cell proliferation, and the inhibition of protein tyrosine kinase, inducing cell apoptosis, were reported with low and high IF doses, respectively [22; 23]. Nowadays, the main dietary source of IFs for humans is soy and derived soy byproducts [24]. Modern western soy transformation processes sometimes expose consumers to high IF concentrations in food [25; 26; 27]. Considering the whole spectrum of effects recorded in humans, this potential dietary exposure may be considered a concern, and the precaution principle should be applied for people who exhibit a particular sensitivity to oestrogens, i.e., infants, children, pregnant women [20] and those with high risk of oestrogen-dependent breast or endometrial cancers. Moreover, hypothyroid patients taking medication, namely levothyroxine, should avoid soy IFs [28; 29]. IFs should instead be kept for natural medication when proven useful. A perfect illustration of this observation can be found in the Chinese pharmacopeia, in which IFs are used for their medicinal properties only as extracted from Kudzu roots [30], with soy never being considered a health ingredient. This is likely because ancient recipes of Asian soy-based food included water soaking, cooking and simmering, a process that removes most IF content, thereby reducing any health impact. Toxicological data have been available since 2008 on genistein (GEN), the most commonly studied phytoestrogen from soy. They were published by the US National Toxicology Program and dealt with the reprorotoxicity [31] and carcinotoxicity [32] of this isoflavue.