- "Tofu Shrinks Brain!" Not a science fiction
scenario, this sobering soybean revelation is for real. But how did the
"poster bean" of the '90s go wrong? Apparently, in many ways
- none of which bode well for the brain.
- In a major ongoing study involving 3,734 elderly Japanese-American
men, those who ate the most tofu during midlife had up to 2.4 times the
risk of later developing Alzheimer's disease. As part of the three-decade
long Honolulu-Asia Aging Study, 27 foods and drinks were correlated with
participants' health. Men who consumed tofu at least twice weekly had more
cognitive impairment, compared with those who rarely or never ate the soybean
- "The test results were about equivalent to what
they would have been if they were five years older," said lead researcher
Dr. Lon R. White from the Hawaii Center for Health Research. For the guys
who ate no tofu, however, they tested as though they were five years younger.
- What's more, higher midlife tofu consumption was also
associated with low brain weight. Brain atrophy was assessed in 574 men
using MRI results and in 290 men using autopsy information. Shrinkage occurs
naturally with age, but for the men who had consumed more tofu, White said
"their brains seemed to be showing an exaggeration of the usual patterns
we see in aging."
- Phytoestrogens - Soy Self Defense
- Tofu and other soybean foods contain isoflavones, three-ringed
molecules bearing a structural resemblance to mammalian steroidal hormones.
White and his fellow researchers speculate that soy's estrogen-like compounds
(phytoestrogens) might compete with the body's natural estrogens for estrogen
receptors in brain cells.
- Plants have evolved many different strategies to protect
themselves from predators. Some have thorns or spines, while others smell
bad, taste bad, or poison animals that eat them. Some plants took a different
route, using birth control as a way to counter the critters who were wont
- Plants such as soy are making oral contraceptives to
defend themselves, says Claude Hughes, Ph.D., a neuroendocrinologist at
Cedars-Sinai Medical Center. They evolved compounds that mimic natural
estrogen. These phytoestrogens can interfere with the mammalian hormones
involved in reproduction and growth a strategy to reduce the number and
size of predators.
- Toxicologists Concerned About Soy's Health Risks
- The soy industry says that White's study only shows an
association between tofu consumption and brain aging, but does not prove
cause and effect. On the other hand, soy experts at the National Center
for Toxicological Research, Daniel Sheehan, Ph.D., and Daniel Doerge, Ph.D.,
consider this tofu study very important. "It is one of the more robust,
well-designed prospective epidemiological studies generally available.
. . We rarely have such power in human studies, as well as a potential
- In a 1999 letter to the FDA (and on the ABC News program
20/20), the two toxicologists expressed their opposition to the agency's
health claims for soy, saying the Honolulu study "provides evidence
that soy (tofu) phytoestrogens cause vascular dementia. Given that estrogens
are important for maintenance of brain function in women; that the male
brain contains aromatase, the enzyme that converts testosterone to estradiol;
and that isoflavones inhibit this enzymatic activity, there is a mechanistic
basis for the human findings." 
- Although estrogen's role in the central nervous system
is not well understood, White notes that "a growing body of information
suggests that estrogens may be needed for optimal repair and replacement
of neural structures eroded with aging."
- One link to the puzzle may involve calcium-binding proteins,
which are associated with protection against neurodegenerative diseases.
In recent animal studies at Brigham Young University's Neuroscience Center,
researchers found that consumption of phytoestrogens via a soy diet for
a relatively short interval can significantly elevate phytoestrogens levels
in the brain and decrease brain calcium-binding proteins. 
- Concerns About Giving Soy to Infants
- The most serious problem with soy may be its use in
infant formulas. "The amount of phytoestrogens that are in a day's
worth of soy infant formula equals 5 birth control pills," says Mary
G. Enig, Ph.D., president of the Maryland Nutritionists Association.
She and other nutrition experts believe that infant exposure to high amounts
of phytoestrogens is associated with early puberty in girls and retarded
physical maturation in boys. 
- A study reported in the British medical journal Lancet
found that the "daily exposure of infants to isoflavones in soy infant-formulas
is 6-11 fold higher on a bodyweight basis than the dose that has hormonal
effects in adults consuming soy foods." (A dose, equivalent to two
glasses of soy milk per day, that was enough to change menstrual patterns
in women. ) In the blood of infants tested, concentrations of isoflavones
were 13000-22000 times higher than natural estrogen concentrations in early
- Soy Interferes with Enzymes
- While soybeans are relatively high in protein compared
to other legumes, Enig says they are a poor source of protein because
other proteins found in soybeans act as potent enzyme inhibitors. These
"anti-nutrients" block the action of trypsin and other enzymes
needed for protein digestion. Trypsin inhibitors are large, tightly folded
proteins that are not completely deactivated during ordinary cooking and
can reduce protein digestion. Therefore, soy consumption may lead to chronic
deficiencies in amino acid uptake. 
- Soy's ability to interfere with enzymes and amino acids
may have direct consequence for the brain. As White and his colleagues
suggest, "isoflavones in tofu and other soyfoods might exert their
influence through interference with tyrosine kinase-dependent mechanisms
required for optimal hippocampal function, structure and plasticity."
- High amounts of protein tyrosine kinases are found in
the hippocampus, a brain region involved with learning and memory. One
of soy's primary isoflavones, genistein, has been shown to inhibit tyrosine
kinase in the hippocampus, where it blocked "long-term potentiation,"
a mechanism of memory formation. 
- Tyrosine, Dopamine, and Parkinson's Disease
- The brain uses the amino acids tyrosine or phenylalanine
to synthesize the key neurotransmitters dopamine and norepinephrine, brain
chemicals that promote alertness and activity. Dopamine is crucial to fine
muscle coordination. People whose hands tremble from Parkinson's disease
have a diminished ability to synthesize dopamine. An increased incidence
of depression and other mood disorders are associated with low levels of
dopamine and norepinephrine. Also, the current scientific consensus on
attention-deficit disorder points to a dopamine imbalance.
- Soy has been shown to affect tyrosine hydroxylase activity
in animals, causing the utilization rate of dopamine to be "profoundly
disturbed." When soy lecithin supplements were given throughout perinatal
development, they reduced activity in the cerebral cortex and "altered
synaptic characteristics in a manner consistent with disturbances in neural
- Researchers at Sweden's Karolinska Institute at the National
Institutes of Health and are finding a connection between tyrosine hydroxylase
activity, thyroid hormone receptors, and depleted dopamine levels in the
brain particularly in the substantia nigra, a region associated with the
movement difficulties characteristic of Parkinson's disease. [11-13]
- Soy Affects the Brain via the Thyroid Gland
- Tyrosine is crucial to the brain in another way. It's
needed for the body to make active thyroid hormones, which are a major
physiological regulator of mammalian brain development. By affecting the
rate of cell differentiation and gene expression, thyroid hormones regulate
the growth and migration of neurons, including synaptic development and
myelin formation in specific brain regions. Low blood levels of tyrosine
are associated with an underactive thyroid gland.
- Scientists have known for years that isoflavones in soy
products can depress thyroid function, causing goiter (enlarged thyroid
gland) and autoimmune thyroid disease. In the early 1960s, goiter and hypothyroidism
were reported in infants fed soybean diets.  Scientists at the National
Center for Toxicological Research showed that the soy isoflavones genistein
and daidzein "inhibit thyroid peroxidase-catalyzed reactions essential
to thyroid hormone synthesis." 
- Japanese researchers studied effects on the thyroid from
soybeans administered to healthy subjects. They reported that consumption
of as little as 30 grams (two tablespoons) of soybeans per day for only
one month resulted in a significant increase in thyroid stimulating hormone
(TSH), which is produced by the brain's pituitary gland when thyroid hormones
are too low. Their findings suggested that "excessive soybean ingestion
for a certain duration might suppress thyroid function and cause goiters
in healthy people, especially elderly subjects." 
- Thyroid Hormones and Fetal Brain Development
- Thyroid alterations are among the most frequently encountered
autoimmune conditions in children. Researchers at Cornell University Medical
College showed that the "frequency of feedings with soy-based milk
formulas in early life was significantly higher in children with autoimmune
thyroid disease."  In a previous study, they found that twice
as many diabetic children had received soy formula in infancy as compared
to non-diabetic children. 
- Recognizing the risk, Swiss health authorities recommend
"very restrictive use" of soy for babies. In England and Australia,
public health agencies tell parents to first seek advice from a doctor
before giving their infants soy formula. The New Zealand Ministry of Health
recommends that "Soy formula should only be used under the direction
of a health professional for specific medical indications. . . Clinicians
who are treating children with a soy-based infant formula for medical conditions
should be aware of the potential interaction between soy infant formula
and thyroid function." 
- Thyroid hormones exert their influence during discrete
windows of time. Inappropriate hormone levels can have a devastating effect
on the developing human brain, especially during the first 12 weeks of
pregnancy when the fetus depends on the mother's thyroid hormones for brain
development. After that, both maternal and fetal thyroid hormone levels
affect the central nervous system.
- A 1999 study published in the New England Journal of
Medicine showed that pregnant women with underactive thyroids were four
times more likely to have children with low IQs if the disorder is left
untreated. The study found that 19% of the children born to mothers with
thyroid deficiency had IQ scores of 85 or lower, compared with only 5%
of those born to mothers without such problems. 
- Thyroid, Brain, and Environmental Toxins
- Children exposed prenatally and during infancy to common
environmental toxins like dioxin and polychlorinated biphenyls (PCBs) can
suffer behavioral, learning, and memory problems because these chemicals
may be disrupting the normal action of thyroid hormone. 
- Soybeans grown in the United States contain residues
of the pesticide dieldrin, an organochlorine similar to DDT. Although both
chemicals were banned in the 1970s, dieldrin still persists in soils and
is absorbed through the roots. Today it is the most toxic residue found
on domestic soybeans.  In Silent Spring, Rachel Carson warned that
dieldrin is nearly 50 times as poisonous as DDT. In addition to disrupting
hormones, it can have long delayed neurological effects, ranging from loss
of memory to mania. 
- Combinations of insecticides, weed killers, and artificial
fertilizers even at low levels have measurable detrimental effects
on thyroid and other hormones as well as on the brain.  EPA scientists
now want to upgrade the commonly used herbicide, atrazine, to a "likely
carcinogen." In animal tests, atrazine attaches to sites on the hypothalamus,
a crucial brain region involved with regulating levels of stress and sex
- Individuals newly diagnosed with Parkinson's disease
were more than twice as likely to have been exposed to insecticides in
their home, compared to those without the disease. 
- Soy formulas for infants can contain other neurotoxins:
aluminum, cadmium, and fluoride. Studies found that aluminum concentrations
in soy-based formulas were a 100-fold greater compared to human breast
milk, while cadmium content was 8-15 times higher than in milk-based formulas.
In an Australian study, the fluoride content of soy-based formulas ranged
from 1.08 to 2.86 parts per million. The authors concluded that "prolonged
consumption (beyond 12 months of age) of infant formula reconstituted with
optimally-fluoridated water could result in excessive amounts of fluoride
being ingested." A study of Connecticut children revealed that mild-to-moderate
fluorosis was strongly associated with soy-based infant formula use. [27-30]
- In May 2000, Boston Physicians for Social Responsibility
released their report, "The Toxic Threats to Child Development."
In the section on neurotoxins, they concluded: "Studies in animals
and human populations suggest that fluoride exposure, at levels that are
experienced by a significant proportion of the population whose drinking
water is fluoridated, may have adverse impacts on the developing brain."
- Iodine vs. Fluorine
- The thyroid gland uses tyrosine and the natural element
iodine to make thyroxine (T4), a thyroid hormone containing four iodine
atoms. The other, much more biologically active thyroid hormone is tri-iodothyronine
(T3), which has three iodine atoms. Lack of dietary iodine has long been
identified as the problem in diminished thyroid hormone synthesis.
- According to the International Council for the Control
of Iodine Deficiency Disorders: "Iodine deficiency has been called
the world's major cause of preventable mental retardation. Its severity
can vary from mild intellectual blunting to frank cretinism, a condition
that includes gross mental retardation, deaf mutism, short stature, and
various other defects. . . The damage to the developing brain results in
individuals poorly equipped to fight disease, learn, work effectively,
or reproduce satisfactorily."
- This crucial role of iodine is another reason why the
thyroid gland is especially vulnerable today. Canadian researcher Andreas
Schuld has documented more than 100 studies during the last 70 years that
demonstrate adverse effects of fluoride on the thyroid gland.  Schuld
says, "Fluorine, being the strongest in the group of halogens, will
seriously interfere with iodine and iodine synthesis, forcing more urinary
elimination of ingested iodine as fluoride ingestion or absorption increases."
- Fluorides were actually used in the past, specifically
to reduce thyroid function. In the 1930s through to the 1960s fluorides
at 0.9mg to 4.5mg/day were given as effective anti-thyroid medication to
hyperthyroid patients."  Russian researchers in the 1980s concluded
that prolonged consumption of drinking water with a raised fluorine content
was a risk factor of more rapid development of thyroid pathology. 
- A major source of fluoride exposure in the United States
is fluoridated drinking water including foods and drinks manufactured
and processed with this treated water. (Only about 5% of the world's population
is fluoridated, and more than half live in North America. 99% of western
continental Europe has rejected, banned, or stopped the addition of fluoride
compounds to their drinking water. ) Also, approximately 45 million
pounds of hydrogen fluoride are released from U.S. coal-fired plants every
year into the environment.
- Soy Phytates Inhibit Zinc Absorption
- Another way that soybeans may affect brain function is
because of their phytic acid content. Phytic acid is an organic acid present
in the outer portion of all seeds. Also known as phytates, they block
the uptake of essential minerals in the intestinal tract: calcium, magnesium,
iron, and especially zinc. According to research cited by the Weston A.
Price Foundation, soybeans have very high levels of a form of phytic acid
that is particularly difficult to neutralize and which interferes with
zinc absorption more completely than with other minerals.
- The soy industry acknowledges the problem, noting that
"one-half cup of cooked soybeans contains one mg of zinc. However,
zinc is poorly absorbed from soyfoods." As for iron, "both phytate
and soy protein reduce iron absorption so that the iron in soyfoods is
generally poorly absorbed." 
- Nutritionist Sally Fallon, author of Nourishing Traditions:
The Cookbook that Challenges Politically Correct Nutrition and the Diet
Dictocrats, says that as early as 1967, researchers testing soy formula
found that it caused negative zinc balance in every infant to whom it was
given. Even when the diets were additionally supplemented with zinc, there
was a strong correlation between phytate content in formula and poor growth.
She warns that "a reduced rate of growth is especially serious in
the infant as it causes a delay in the accumulation of lipids in the myelin,
and hence jeopardizes the development of the brain and nervous system."
- Zinc and the Brain
- Relatively high levels of zinc are found in the brain,
especially the hippocampus. Zinc plays an important role in the transmission
of the nerve impulse between brain cells. Deficiency of zinc during pregnancy
and lactation has been shown to be related to many congenital abnormalities
of the nervous system in offspring. In children, "insufficient levels
of zinc have been associated with lowered learning ability, apathy, lethargy,
and mental retardation." 
- The USDA references a study of 372 Chinese school children
with very low levels of zinc in their bodies. The children who received
zinc supplements had the most improved performance especially in perception,
memory, reasoning, and psychomotor skills such as eye-hand coordination.
Three earlier studies with adults also showed that changes in zinc intake
affected cognitive function. 
- New research has identified a specific contingent of
neurons, called "zinc-containing" neurons, which are found almost
exclusively in the forebrain, where in mammals they have evolved into a
"complex and elaborate associational network that interconnects most
of the cerebral cortices and limbic structures." This suggests the
importance of zinc in the normal and pathological processes of the cerebral
cortex.  Furthermore, age-related tissue zinc deficiency may contribute
to brain cell death in Alzheimer's dementia. 
- Safe Soy
- To produce soy milk, the beans are first soaked in an
alkaline solution, then heated to about 115 degrees C in order to remove
as much of the trypsin inhibitors as possible. Fallon says this method
destroys most, but not all of the anti-nutrients, however it has the "unhappy
side effect of so denaturing the proteins that they become very difficult
to digest and much reduced in effectiveness." Furthermore, phytates
remain in soy milk to block the uptake of essential minerals.
- Only a long period of fermentation will significantly
reduce the phytate content of soybeans, as well as the trypsin inhibitors
that interfere with enzymes and amino acids. Therefore, fermented soy products
such as tempeh and miso (not tofu) provide nourishment that is easily assimilated.
- Links to Further Information Soy Online Service Weston
A. Price Foundation
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J Am Coll Nutr 2000 Apr;19(2):242-55.
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