Phytoestrogens & Cognitive Function

Do soy phytoestrogens rot the brain?

Do soy phytoestrogens rot the brain?  USFDA researcher Dr Dan Sheehan of the National Centre for Toxicological Research thinks it might.

You can read more on how tofu consumption results in accelerated brain aging, reduces cognitive function and is associated with Alzheimer's disease at the Star Bulletin which reports on Lon White's latest findings.

The hippocampus is the area of the brain that is vital for learning and short-term memory.  Research by O'Dell shows that genistein inhibits development of this brain function. 

See also "Is there a reason to believe Tofu may cause brain atrophy" by Ian Williams Goddard and The trouble with tofu: soy and the brain by John D MacArthur ( http://www.brain.com/cgi-bin/Brain.storefront/3c4382c3004dcff4271fc0a80a0c06a6/UserTemplate/26?id=13500&cat_id=37 ) This article is also found on the Mercola website.

Further Reading

Evidence for genistein mediated cytotoxicity and apoptosis in rat brain.
Choi EJ, Lee BH; Life Sci. 2004 Jun 11;75(4):499-509.

The high dose of genistein (20 mg/day) significantly increased lactate dehydrogenase (LDH) in rat brain tissue homogenates, whereas the low dose of genistein (2 mg/day) decreased LDH. In addition, DNA fragmentation was detected in homogenates of brain tissue from rats receiving either dose of genistein. These results are consistent with those of in vitro studies indicating that high concentrations of genistein caused cytotoxicity and DNA ladder formation in primary cultures of cortical neurons.

These results suggest that chronic administration of genistein at high doses may induce cytotoxicity and apoptosis in the rat brain.

Full Abstract Here

Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial.
Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, Lampe JW, van der Schouw YT; JAMA. 2004 Jul 7;292(1):65-74.

This double-blind randomized trial does not support the hypothesis that the use of soy protein supplement containing isoflavones improves cognitive function, bone mineral density, or plasma lipids in healthy postmenopausal women when started at the age of 60 years or later.

Full Abstract Here

In short - soy Protein and Isoflavones do not improve cognitive function

Increased aggressive behavior and decreased affiliative behavior in adult male monkeys after long-term consumption of diets rich in soy protein and isoflavones.
Simon NG, Kaplan JR, Hu S, Register TC, Adams MR., Horm Behav. 2004 Apr;45(4):278-84.

In the monkeys fed the higher amount of isoflavones, frequencies of intense aggressive (67% higher) and submissive (203% higher) behavior were elevated relative to monkeys fed the control diet (P's < 0.05). In addition, the proportion of time spent by these monkeys in physical contact with other monkeys was reduced by 68%, time spent in proximity to other monkeys was reduced 50%, and time spent alone was increased 30% (P's < 0.02).

Full Abstract Here

New Findings May Support Soy-Dementia in Men
Article by Ian Williams Goddard, August 9, 2003

Brain Aging and Midlife Tofu Consumption
Lon R. White, MD, MPH,,,, Helen Petrovitch, MD,, G. Webster Ross, MD,, Kamal Masaki, MD,, John Hardman, MD, James Nelson, MD, Daron Davis, MD and William Markesbery, MD. Journal of the American College of Nutrition, Vol. 19, No. 2, 242-255 (2000).

Poor cognitive test performance, enlargement of ventricles and low brain weight were each significantly and independently associated with higher midlife tofu consumption.

Conclusions: In this population, higher midlife tofu consumption was independently associated with indicators of cognitive impairment and brain atrophy in late life.

Full Abstract Here, Full Paper Here

A convincing hypothesis to explain the premature brain-aging effects of soy and the Hawaii Aging study results is available Here.

Soya phytoestrogens change cortical and hippocampal expression of BDNF mRNA in male rats.
File SE, Hartley DE, Alom N, Rattray M. Neurosci Lett. 2003 Feb 27;338(2):135-8.

Using in situ hybridisation, significant reductions were found in brain-derived neurotrophic factor (BDNF) mRNA expression in the CA3 and CA4 region of the hippocampus and in the cerebral cortex in the rats fed the diet containing phytoestrogens, compared with those on the soya-free diet.

Full Abstract Here,

This paper provides interesting reading when put into the context of the following paper.

Brain-derived neurotrophic factor is reduced in Alzheimer's disease.
Connor B, Young D, Yan Q, Faull RL, Synek B, Dragunow M. Brain Res Mol Brain Res. 1997 Oct 3;49(1-2):71-81.

Consistent with this hypothesis, a reduction in BDNF mRNA expression has been observed in human post-mortem Alzheimer's disease hippocampi.

We observed a reduction in the intensity and number of BDNF-immunoreactive cell bodies within both the Alzheimer's disease hippocampus and temporal cortex when compared to normal tissue. These results support and extend previous findings that BDNF mRNA is reduced in the human Alzheimer's disease hippocampus and temporal cortex, and suggest that a loss of BDNF may contribute to the progressive atrophy of neurons in Alzheimer's disease.

Full Abstract Here

The soya isoflavone content of rat diet can increase anxiety and stress hormone release in the male rat.
Hartley DE, Edwards JE, Spiller CE, Alom N, Tucci S, Seth P, Forsling ML, File SE. Psychopharmacology (Berl) 2003 Mar 5;

Isoflavones form one of the main classes of phytoestrogens and have been found to exert both oestrogenic and anti-oestrogenic effects on the central nervous system. The effects have not been limited to reproductive behaviour, but include effects on learning and anxiety and actions on the hypothalamo-pituitary axis. It is therefore possible that the soya content of diet could have significant effects on brain and behaviour and be an important source of between-laboratory variability.

Compared with the rats fed the iso-free diet, the rats fed the iso-150 diet spent significantly less time in active social interaction and made a significantly lower percentage of entries onto the open arms of the plus-maze, indicating anxiogenic effects in both animal tests. The groups did not differ in their basal corticosterone concentrations, but the iso-150 group had significantly elevated stress-induced corticosterone concentrations. Stress-induced plasma vasopressin concentrations were also significantly elevated in the iso-150 diet group compared with the iso-free rats.

Major changes in behavioural measures of anxiety and in stress hormones can result from the soya isoflavone content of rat diet. These changes are as striking as those seen following drug administration

Full Abstract Here

Neurobehavioral effects of dietary soy phytoestrogens.
Lephart ED, West TW, Weber KS, Rhees RW, Setchell KD, Adlercreutz H, Lund TD.  Neurotoxicol Teratol 2002 Jan-Feb;24(1):5-16

These results indicate that consumption of dietary phytoestrogens resulting in very high plasma isoflavone levels (in many cases over a relatively short interval of consumption in adulthood) can significantly alter sexually dimorphic brain regions, anxiety, learning and memory. The findings of these studies identify the biological actions of phytoestrogens, specifically isoflavones and their metabolites, found in animal soy-containing diets on brain and behavior and implicate the importance of phytoestrogens given the recognized significance of estrogens in brain and neural disorders, such as Alzheimer's disease, especially in women.

Full Abstract Here

Effect of estradiol and soy phytoestrogens on choline acetyltransferase and nerve growth factor mRNAs in the frontal cortex and hippocampus of female rats.
Pan Y, Anthony M, Clarkson TB.  Proc Soc Exp Biol Med 1999 Jun;221(2):118-25

Our data suggest that soy phytoestrogens may function as estrogen agonists in regulating ChAT and NGF mRNAs in the brain of female rats.

Full Abstract Here

Dietary soy phytoestrogen effects on brain structure and aromatase in Long-Evans rats.

Lephart ED, Adlercreutz H, Lund TD. Neuroreport 2001 Nov 16;12(16):3451-5

Since most commercial animal diets contain significant concentrations of phytoestrogens their influence on brain structure should be considered.

Full Abstract Here