FINDINGS MAY SUPPORT SOY-DEMENTIA CORRELATION IN MALES
(c) 08/06/03 - Ian Williams Goddard
In April 2000, Lon White and others reported a dose-dependent positive
correlation between tofu consumption and brain atrophy in a large
sample of men over several decades.  While correlation does not
prove causation, study size and duration along with the robust
dose-dependent relationship caused me, even as a vegetarian, to avoid
tofu and other soy products.
Correlation-based hypotheses should be tested against the availability
of possible causal mechanisms. In addition to possible causal
mechanisms previously cited by this author,  recent findings
significantly increase the case for a causal mechanism of soy-induced
Pro-Atrophy Pharmacology Indicated
Brain-derived neurotrophic factor (BDNF) facilitates the survival and
genesis of brain cells. [3-4] The neuroprotective effects of caloric
restriction are attributed in part to increased BDNF.  On the other
hand, reduced BDNF is known to cause brain-cell atrophy and is
associated with Alzheimer's disease. [6-7] Now, a study in
"Neuroscience Letters" reports that soy significantly reduced BDNF in
the hippocampus and cerebral cortex of male rats.  Since reduced
BDNF can cause neural atrophy, these findings appear to provide
compelling evidence for a causal mechanism that might explain the
positive correlation between tofu (soy) consumption and brain atrophy
demonstrated by White et al. 
Bad For Boys, Good For Girls?
While soy appears to reduce BDNF in male rats, it has also been shown
to increase BDNF in female rats.  In fact, soy appears to affect
neurological parameters in a sex-defined fashion wherein females
benefit and males suffer. [10-13] There is little doubt among
researchers that this is because soy is high in phytoestrogens, which
are plant-derived substances that act like the female hormone
However, that sex-defined difference fails to explain the findings
regarding the wives of male subjects in White et al, who reported: "A
similar association of midlife tofu intake with poor late life
cognitive test scores was also observed among wives of cohort members,
using the husband's answers to food frequency questions as proxy for
the wife's consumption."  White et al proposed that long-term
consumption of weaker soy estrogens may displace the body's own
stronger estrogen along with its benefits.
Evidence Against Soy-Dementia Hypothesis?
A possible signal contrary to a soy-dementia link is the low
prevalence of dementia  and high consumption of soy in Okinawa,
Japan.  However, that negative correlation, like any correlation,
does not prove causation. For example, perhaps soy does cause dementia
but other factors in Okinawa offset the effect.
Also, White et al explored correlations of a range of foods to
neurological parameters, whereas this Okinawa analysis is a sweeping
generalization of only tofu to all of Okinawa. In other words, it
stands to reason that the study by White et al finding a positive
tofu-dementia correlation has the greater likelihood of providing the
more accurate picture. Nevertheless, in my view this Okinawa data
warrants further examination as a possible route to falsifying the
In closing, the findings of soy-induced BDNF reduction in male rat
brain regions that are central to the onset of dementia, in addition
to previous findings,  appear to provide compelling evidence of a
possible causal mechanism that might explain the soy-dementia
correlation reported by White et al.  Obviously further research is
necessary before a clear picture emerges regarding the effects of
long-term soy consumption on the brain. But in the meantime, my
inclination is to play it safe and avoid soy.
 White et al: "In this population, higher midlife tofu consumption
was independently associated with indicators of cognitive impairment
and brain atrophy in late life."
 Goddard (scroll to): "Is There Reason to Believe Tofu May Cause
Brain Atrophy?" http://iangoddard.net/soy.htm
 Exp Neurol (Sep 2002): "Neurotrophic factors have long been known
to promote neuronal survival and differentiation."
 J Neurochem (Sep 2002): "These findings suggest that BDNF plays an
important role in the regulation of the basal level of neurogenesis in
dentate gyrus of adult mice [...]."
 Endocrinology (Jun 2003): "Recent studies have shown that DR
[dietary restriction] stimulates the production of brain-derived
neurotrophic factor (BDNF) in brain cells, which may mediate
neuroprotective and neurogenic actions of DR."
 Arch Gen Psychiatry (Jul 1997): "stress can decrease the
expression of brain-derived neurotrophic factor and lead to atrophy of
these same populations of stress-vulnerable hippocampal neurons."
 Brain Res Mol Brain Res (Oct 3, 1997): "a reduction in BDNF mRNA
expression has been observed in human post-mortem Alzheimer's disease
hippocampi. [...] 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 loss of BDNF may contribute to
the progressive atrophy of neurons in Alzheimer's disease."
 Neurosci Lett (Feb 27, 2003): "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
[male] rats fed the diet containing phytoestrogens, compared with
those on the soya-free diet."
 Neurosci Lett (Feb 1999): "soy phytoestrogens significantly
increased the mRNA levels of BDNF [...in] female rats."
 Neurotoxicol Teratol (Jan-Feb 2002): "when learning and memory
parameters were examined in a radial arm maze testing visual-spatial
memory (VSM), the diet treatments significantly changed the typical
sexually dimorphic pattern of VSM. Specifically, adult Phyto-rich fed
females outperformed Phyto-free fed females, while in males on the
same diets, the opposite pattern of maze performance was observed."
 BMC Neurosci (2001 2(1):20): "Female rats receiving lifelong
exposure to a high-phytoestrogen containing diet (Phyto-600) acquired
the maze faster than females fed a phytoestrogen-free diet
(Phyto-free); in males the opposite diet effect was identified. [...]
These findings suggest that dietary soy derived phytoestrogens can
influence learning and memory and alter the expression of proteins
involved in neural protection and inflammation in rats."
 BMC Neurosis (2001 2(1):21): "When a diet change was initiated in
adulthood, control phytoestrogen-rich fed females outperformed control
females switched to a phytoestrogen-free diet. Whereas, in control
males the opposite diet effect was identified. "
 Neurosci Lett (May 15, 2003): "This study is the first to show
that lifelong consumption of dietary phytoestrogens alters the HPA
stress response in male rats."
 Dementia: http://okinawaprogram.com/images/dem.gif
 Soy intake: http://okinawaprogram.com/images/ment.gif
Some alternative views on soy:
"To lengthen thy life, lessen thy meals." Ben Franklin
Ongoing CR-monkey-study update: "In the monkeys...those on
reduced feeding since the study started are dying at a rate
that is about half that of the monkeys receiving a full food
ration." Associated Press: Eating less may extend human life.
August 1, 2002 : http://www.msnbc.com/news/788746.asp?0si=-