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. [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/q...&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/q...&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/q...&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/q...&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/q...&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/q...&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/q...&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/q...&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/q...&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/q...&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/q...&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 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=-

Ian Goddard <igoddard@erols.mom> wrote:

Frequently aluminium sulphate or alum is illicitly included in the
coagulant used to gell the soy. The addition of aluminium helps to
give the tofu a much firmer texture.

Surely this must complicate any statistical research demonstrating
neurotoxicity of Tofu products.

Bob M

<snip>

How common is this problem in Japan?

Tofu and miso are two staples of that land, so if there is a problem it
should be evident in that country.


--
to email me
Please remove "all your clothes"

Doug

Ian Goddard <igoddard@erols.mom> wrote in message news:<0v53jvsnc8c06r4jbe8030jfo6ostlegvg@4ax.com>. ..

also check this out:

http://www.mercola.com/2000/oct/8/soy_crisis.htm

Dr. Joseph Mercola in the above article refers to reason for high
Aluminium in soy as follows:

"In addition, soy milk is high in aluminium. That's because the soy
protein isolate it's made from is acid-washed in aluminium tanks. No
wonder it tastes bad. "

-Anatoly

molab@ww.co.nz (R Molony) wrote:


IAN: I doubt it. William Harris explored the question of
aluminum's possible role in the findings of White et al:
http://www.vegsource.com/harris/brain_aging.htm

He had 16 soy products assayed for Al. Sure enough tofu
was on the high side, at 15.99 parts per million. However,
in the big picture that is not very remarkable. That's
16 micrograms of Al per gram of tofu. Estimates of daily
dietary Al intake range from 1.53 to 160 mg per person:
http://www.inchem.org/documents/jecf...no/v12je04.htm

So you'd have to eat about 2.2 lbs tofu/day to match the
high-end estimate of normal daily Al intake. Given that
White et al defined the high-end of tofu intake as two
or more servings per week, that would be below 2 lbs/day!
And most likely "servings" among this Japanese American
cohort probably means meals wherein tofu is a component.

That's not to say Al may not play a role in neurological
degeneration. I've posted a lot of evidence that it does:
http://www.google.com/groups?selm=gq...1n%404 ax.com

But given that there are many foods with as much or more
Al content than tofu as measured by Harris, and that
White et al tested ALL foods reported by the cohort and
only tofu produced a loud & clear statistically significant
correlation to indicators of cognitive impairment and brain
atrophy, it stands to reason Al not producing that signal.

http://IanGoddard.net/journal.htm

"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=-

"Doug" <doug_adam@allyourclothesglobal.net.au> wrote:


IAN: But tofu isn't a Japanese "staple." According
to Dr Mercola: "the Japanese don't eat that much soy:
a 1998 study showed that a Japanese man typically eats
about 8g (2 tsp) a day, nothing like the 220g (8oz) that
a Westerner could put away by eating a big chunk of tofu
and two glasses of soy milk." Link posted by Anatoly:
http://www.mercola.com/2000/oct/8/soy_crisis.htm

While Alzheimer's disease is more common and vascular
dementia less common among Japanese Americans than among
native Japanese,[*] that doesn't tell us anything about
tofu's relationship to dementia. You'd have to examine the
relationship between dementia and tofu (soy) consumption
in Japan, controlling for various facts as White et al
did in the Japanese American cohort they examined.
[*]
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

http://IanGoddard.net/journal.htm

"Our greatest illusion is to believe that we are what
we think ourselves to be." Henri Amiel (1821-1881)

Tsu Dho Nimh <tsudhonimh@lumbercartel.com> wrote:

But it's still METAL, and an even heavier metal than aluminium. It
must be bad, especially if it gets into the mouth, where no metals
should go.

--
Peter Bowditch peterb@ratbags.com
The Millenium Project http://www.ratbags.com/rsoles
The Green Light http://www.ratbags.com/greenlight
I'm a Bright. Are you?

White et al: http://www.jacn.org/cgi/content/full/19/2/242

Posted this elsewhere (CR means caloric restriction):

IAN: Here's a rebuttle to White et al followed by their
responce: http://www.jacn.org/cgi/content/full/19/4/467

As I've noted, laboratory findings are also relevent. The
soy phytoestrogen genistein inhibits DNA synthesis in rat
cerebral cortex and suppresses a range of neurotrophic
(neuroprotective) factor functions. An important example:

J Neurochem (Oct 1995): "The ability of the neurotrophic
factors to suppress glutamate toxicity and glutamate-induced
peroxide accumulation [in hippocampal neurons] was attenuated
by the tyrosine kinase inhibitor genistein, indicating the
requirement for tyrosine phosphorylation in the neuro-
protective signal transduction mechanism."

http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

"Attenuated" of course means "reduced." Genistein reduced a
critical antiaging function. In fact, it's well-known that the
chemical class to which genistein is a member, tyrosine kinase
inhibitors, interfere with neurotrophic (neuroprotective)
factors as a class trait. If CR is neuroprotective because it
raises neurotrophic factors, the same logic suggests that soy
could be neurotoxic for inducing the opposite (even if only in
males). In short, the known effects of soy phytochemicals point
to a prediction of brain atrophy. In my view, that adds weight
to the soy-dementia correlation reported by White et al.

http://IanGoddard.net

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

"Ian Goddard" <igoddard@erols.mom> wrote in message
news:0v53jvsnc8c06r4jbe8030jfo6ostlegvg@4ax.com...
This is a nagging question for me also. I'm a vegetarian
also, and I used to regard soy beans and products made
from soy beans as ideal legumes and products made
from legumes. (Soy beans have a large amount of iron,
protein, and fiber per calorie.) I have largely eliminated
tofu, but I still consume soy milk, tempeh, and soy beans.
Perhaps I should stop consuming these foods also. This
thread may help me make that decision.

Is it correct to equate tofu and other soy products (beans
and tempeh, for example)? What form of soy was used in
the rat study you cite?

I think I recall that the wives of the men studied
in Hawaii also experienced dose-dependent cog-
nitive slippage. (That study used tofu).

Yes, this is what I referred to above.

Could it be (I have my fingers crossed) that the
problem lies in the tofu process rather than the bean?

George


__________________________________________________ _____________________

Dr. Michael Lam, MD, www.drlam.com, himself an Asian, has long
recommended against all soy except for fermented soy products, tempeh
and miso. Dr. Dean Ornish has recently sent an advisory suggesting
that males following his diet structure may wish to eliminate soy from
the diet and Dr Andrew Weil, has recently pulled back from an
enthusiastic endorsement of all soy products to cautious "one cup of
soy milk should be OK".

I have a possible pre-cancerous condition of the prostate (3-clean
biopsies in the last 8 years)that I think my substitution of soy (meat
substitutes and milk)has helped me with. As I exersize hard, I find I
must have a good protein source. Vitamin Shoppes has a non-soy
protein powder, but the problem with this is that it is expensive,
$14/lb., and that much of its protein is derived from legumes, which
may replicate the soy problems. Misos may all be too salty and tempeh
has a taste problem for me. Perhaps egg-whites and a return to some
milk are what I must do. It isn't easy.

"Rob" <robwid3000@hotmail.com> wrote in message
news:250fb761.0308101155.1c6fc039@posting.google.c om...
Have you given whey protein isolate a try? While I don't use it
exclusively, I've been using it to increase my protein intake without some
of the problems possibly associated with increasing other sources of
protein. It doesn't taste bad, isn't really high in calories, & doesn't
cost an arm & a leg.

Michele
I ENJOY being a cranky bitch.

tcarter2@elp.rr.com (Thomas Carter) wrote:

IAN: Well, your conclusions certainly supported your bias.



IAN: This is the Table 1 title: "Characteristics at Baseline and
at the Time of Cognitive Assessment, according to Response at
Baseline to the Question: 'How Often do You Eat Tofu?'"
http://www.jacn.org/cgi/content/full/19/2/242/T1



IAN: It says, "CASI score adjusted for age (single year) and
years of schooling completed." As such, it need NOT be 2.6%.
So you base the charge of "data doctoring" on your assumption
that the figure "probably" should have adjusted to some number
other than 2%. What a flimsy basis for such a harsh accusation!




IAN: Frankly, I don't believe your "quick glance" supercedes
the expertise of eight professional epidemeologists who spent
years examining all the data. Frankly, that you believe you
can debunk these experts in a few moments speaks for itself.
Moreover, that in a few moments you feel qualified to accuse
these professionals of "data doctoring" because some numbers
are "probably" not what you think they should be is outrageous.




IAN: That's a cross-sectional, not longitudinal, analysis,
so you can't really say, "As the members get older this
failure rate is gradually reduced," since each stratified
group represents a different set of people. The important
point is the sixth grouping showing the overall relation:

http://www.jacn.org/cgi/content/full/19/2/242/F2



IAN: But the study states: "The CASI has been validated as
a screening instrument for dementia in the United States
and Japan, in both English and Japanese languages. [...]
participants selected either Japanese or English for testing,
depending on the language with which they were most comfortable."

So your conclusion that scores were biased by native education
stands in direct opposition to information provided in the study.



IAN: That's irrelevant due to your oversight noted above.



IAN: That's a false assumption based on your oversight above.

Frankly, I just don't have time to respond point-by-point.
Given that you're asking us to believe your personal analysis
and thereby doubt eight expert epidemiologists and their peer-
reviewers, it's fair to ask: exactly what are your credentials?
I don't care for appeals to authority, but regarding complex
statistical data analyses, expertise really means something.

One last comment:



IAN: So there IS a relation to smaller brain size and tofu
(which was the primary focus of my post), but alas you've
determined that it is a result of methionine deficiency.
http://www.jacn.org/cgi/content/full/19/2/242/F3 You know,
you could broach your comments as hypotheses and questions,
rather than, as you have, accusations of "data doctoring" and
firm conclusions of "fatal mistakes" and such by the authors
that you use to caste sweeping aspersion on peer-review per se.
Moreover, you should locate and ask the authors directly before
posting public accusations against their expertise and honor.

http://IanGoddard.net/journal.htm

"Our greatest illusion is to believe that we are what
we think ourselves to be." Henri Amiel (1821-1881)