Soy Neurotoxicity?

[Guest guest]

FINDINGS MAY SUPPORT SOY-DEMENTIA CORRELATION IN MEN

© 08/06/03 - Ian 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. [1] 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, [2] recent findings

significantly increase the case for a causal mechanism of soy-induced

brain atrophy.

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. [5] 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. [8] 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. [1]

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. [9] 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

estrogen.

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. " [1] 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 [14] and high consumption of soy in Okinawa,

Japan. [15] 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

soy-dementia hypotheses.

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, [2] appear to provide compelling evidence of a

possible causal mechanism that might explain the soy-dementia

correlation reported by White et al. [1] 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.

_______________________________________________________________________

[1] White et al: " In this population, higher midlife tofu consumption

was independently associated with indicators of cognitive impairment

and brain atrophy in late life. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

0763906 & dopt=Abstract

[2] Goddard (scroll to): " Is There Reason to Believe Tofu May Cause

Brain Atrophy? " http://iangoddard.net/soy.htm

[3] Exp Neurol (Sep 2002): " Neurotrophic factors have long been known

to promote neuronal survival and differentiation. "

http://www.neuro.mpg.de/research/csn/bdnf_ltp

[4] 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 [...]. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

2354284 & dopt=Abstract

[5] 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. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

2746306 & dopt=Abstract

[6] 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. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=9\

236543 & dopt=Abstract

[7] 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. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=9\

387865 & dopt=Abstract

[8] 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. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

2566171 & dopt=Abstract

[9] Neurosci Lett (Feb 1999): " soy phytoestrogens significantly

increased the mRNA levels of BDNF [...in] female rats. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

0081916 & dopt=Abstract

[10] 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. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

1836067 & dopt=Abstract

[11] 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. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

1801187 & dopt=Abstract

[12] 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. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

1801188 & dopt=Abstract

[13] 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. "

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

2727319 & dopt=Abstract

[14] Dementia: http://okinawaprogram.com/images/dem.gif

[15] Soy intake: http://okinawaprogram.com/images/ment.gif

Some alternative views on soy:

http://www.soyonlineservice.co.nz

http://www.healingcrow.com/soy/soy.html

http://IanGoddard.net/journal.htm

" To lengthen thy life, lessen thy meals. " Ben lin

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=-