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Figure 3. Isoflavones in advanced clinical trials

or apoptosis, which makes it very difficult to predict its chemopreventive or therapeutic intervention
[65]
effect . Additionally, adequate analytical techniques such as HPLC/MS/MS for proper quantification of
phytoestrogen in a plant/food matrix, assessment of its pharmacokinetic parameters from serum analysis
and also systemic metabolite determination, have become available relatively recently. When the major FDA
decision concerning soy nutrient was undertaken, recommending everyday 25 g soy protein administration
for cholesterol level control, neither proteins nor isoflavones which it contained, were specified .
[66]
Currently, when any plant-derived material can be analyzed with great accuracy, soy protein isolates and
concentrates, with varying isoflavone content declared, remain in the segment of nutraceuticals with
countless estrogenic preparations based on herbal extracts. Soy is grown in huge amounts of 300 million
tons harvested annually, which contains at least 1 g of isoflavone fraction per kilogram of crop. Numerous
technical processes allowing for isoflavone isolation exist, practically ready for implementation [25-27] .
Nevertheless, medicinal research materials, which are on a drug candidate evaluation path towards clinical
trials (aiming at validation of isoflavones as preventive or therapeutic agents in bone health, oncological
problems or neurodegeneration) are recently more often synthetic than of natural origin. Thus, synthetic
TM
genistein (Bonistein ) was registered for assistance of bone health and to stop bone loss in postmenopausal
[67]
women . As a phytoestrogen, genistein have been validated for a number of targets other than ER, such as
[68]
NF-κB, EGFR, CDK, KIF20A, PLK1, and AR, in molecular and cellular models . Even at that preclinical
level, there are inconsistencies in results of cell cycle arrest, kinase inhibition data and proliferation of cells
[65]
with various ER status . Genistein has been the subject of many randomized clinical trials in connection
with postmenopausal health, various cancers and neurodegenerating San Filippo disease, which is
[69]
[70]
genetically conditioned faulty storage of glycosaminoglycans [Figure 3].
New hurdles appear when it comes to clinical trials, plagued by problems of low isoflavone solubility and
bioavailability, and high genetic as well as metabolic variety among clinical trial participants. Generally,
there seems to be a problem of design and crisis of credibility in clinical trials, which affects many drug
candidates from the phytochemical pool, especially in the anticancer field [64,65,68] . Soy products for human
food use are generally considered beneficial for health, although some controversies concerning its
estrogenic effects persist. Technically, soy isoflavone-free products could be obtainable by relatively minor
soybean process modifications but GRAS status and good market standing of soy nutraceuticals provide
arguments against such decision. Reflection on advancement of evidence-based medicine requirements
seem to indicate that the chances of further progress of soy isoflavone phytoestrogens towards registered
medicine status are very slim; on the other hand, their existence among nutraceuticals and on the
complementary and alternative medicine market is unquestionable. Also, rational nutrition is a large forum
for innovation aiming at improvement of healthcare by prevention rather than therapeutic intervention.

Nutrition habits are already considerably influenced by the availability of high-quality scientific knowledge
obtainable through the internet and open sources. Future food choices undoubtedly are going to reflect