Genistein

The effects of genistein are very complex and the ideal dosage is a topic of great debate, with the range of possibilities rather dramatic. There is evidence that genistein can cross the blood-brain barrier based on in vivo animal studies⁷, and it has been shown to have significant effects on the invasiveness of GBM cells in vitro.⁸

From a wide variety of studies, genistein has been shown to:

• Inhibit tyrosine kinase, specifically EGF
• Inhibit protein kinase C
• Inhibit the fatty acid amide hydrolase (FAAH)
• Inhibit topoisomerase II
• Act as an antioxidant
• Compete for estrogen receptors
• Induce the NAG-1 anti-inflammatory gene
• Promote cell apoptosis
• Induce p21 and p53
• Downregulate the MDM2 oncogene
• Reduce malignancy proliferation
• Reduce LDL cholesterol¹
• Downregulate osteoclasts, thereby minimizing bone loss in the menopausal period¹
• Increase cytoxicity of BCNU and other chemo agents
• Enhances the anti-cancer effects of indole-3-carbinol (I3C)

Some or all of genistein's effects may be the result of the same primary action.

Genistein has one of the most complicated stories of any substance when it comes to cancer prevention and treatment. No single study or researcher seems to have a full and complete understanding of how genistein works and when and how much it should be consumed for its anti-cancer properties. And the ideal daily dosage for brain tumor patients is completely unclear.

What is clear is that normal dietary quantities of soy products result in significantly lower rates of certain cancers, especially breast cancer¹. At this time, there does not appear to be any dose escalation/benefit studies with genistein. An interesting research project would be to run through the dozens of genistein studies and find the average quantities and plasma levels used.

A 1995 study in the Journal of Nutrition reported that most of genistein's effects on malignant cells did not occur at normal plasma concentrations (< 5 mcg/mL).

However, an in vitro 2002 study using human and rat GBM cell lines reported significant effects from genistein in combination with BCNU "at a concentration typical of plasma levels following soy diet intake."⁴ Patients using BCNU (carmustine), which is the active chemo agent in Gliadel Wafers, will be curious to note that this study reported that genistein can "significantly enhance the antiproliferative and cytotoxic action of BCNU."

Ben Williams, the well-known GBM survivor and author of Surviving "Terminal" Cancer, as well as others, hypothesize that consumption of large quantities of genistein--far beyond what a normal soy diet provides--may provide the most benefit. Sources of extracted genistein are few and far between, but the Life Extension Foundation has a variety of products containing the largest quantities of genistein found on the market, including their "Ultra Soy" product, which is extremely expensive (over $250 per bottle).

There are a few indications that some or all of the benefits of genistein are dependent on the status of the tumor suppressor protein p53. Some of genistein's anti-cancer properties appear to be more effective with mutant and wild-type versions of this protein. However, a 2005 study at Univ. of Alabama (a U.S. brain tumor SPORE site) found that genistein's induction of apoptosis occurred regardless of p53 status.

On the negative side, genistein has been shown to stimulate the growth of estrogen-dependent breast cancer tumors. About 60% of premenopausal and 75% of postmenopausal breast cancer patients have estrogen-dependent tumors. It appears that genistein stimulates their growth by increasing the activity of aromatase, an enzyme that synthesizes estrogen. Aromatase is also produced in the brain and at least one study has suggested that it could possibly play a role in glioma proliferation, however, other studies have shown that glioma cells have few or no estrogen receptors. This is a subject that needs to be further researched, which may even be possible with existing data.

Some urban myths have also surfaced as a result of the weak phytoestrogen properties of genistein. While some studies have shown that consumption of soy products can slightly increase the duration of a woman's menstrual cycle, this effect is actually beneficial in preventing cancer, because it lowers a woman's risk of breast cancer. Furthermore, a large study at the University of Pennsylvania which followed a group of men and women for up to 35 years looked at possible health or reproductive ramifications of exposure to soy-based formula in infancy. They found no differences between those who consumed soy-based formula vs. those who consumed a cow milk formula.³

An interesting Spanish study in 2007 reported that while genistein did not increase brain perfusion (blood flow), two other isoflavones did without any increase in blood pressure: daidzein and biochanin A. This study was based on in vivo rat studies, and it is unclear what effect increased brain perfusion might have in a human brain tumor patient, noting the danger of hemorrhages yet the benefit of oxygenation of hypoxic tumors.⁵ Tumor oxygenation, as measured by EF5 binding, corresponds to tumor grade and aggressiveness, with glioblastoma showing the highest degree of hypoxia.⁶

In balance, while genistein has been shown to stimulate existing tumor growth in a very specific type of breast cancer, the wide range of its anti-cancer properties, the tremendous quantity of in vitro studies, and the benefits proven in huge epidemiological studies, all advocate its use in both cancer prevention and treatment.

Because genistein has so many potential impacts on malignant cells, the variety and degree of its effects may be dose dependent, cancer type-dependent, patient-dependent, and/or gene expression dependent. It's a complicated picture.

For brain tumors, genistein is extremely promising but there needs to be more studies specifically demonstrating its effects with brain tumors.