FDA scientists questions soy safety - but where is GM testing?


Thanks to Richard & Valerie James in New Zealand for alerting us to the ABC
News article below.

If this kind of thing is cropping up with research on normal soya which
requires no special testing for release onto the market, how come the
allegedly thorough testing with GM varieties has not shown any similar
adverse effects on animal and human health?

This raises the question:

"Is the right kind of testing on GM soy being done, or are the testing
methods used not suited for picking up health effects?"

The adverse effects from normal soy claimed here should be showing up in GM
soy as well if GM soy is really "substantially equivalent" to normal soy as
claimed by food safety regulators around the world.

Because the GM testing appears not be successfully identifying these known
problems, this situation would appear to be further evidence that GM soya
has only been subject to superficial testing. If so what additional effects
created by the genetic modification have also gone undetected?

This situation is especially significant because outstanding questions
concerning the safety of normal soy appear to be arising even from within
the US Food and Drug Administration (FDA) itself. According to the ABC News
report
below soy safety questions from recent research have arisen in relation to a
number of health problems including breast cancer in women, brain function
in men, and developmental abnormalities in children.

According to the FDA scientists concerned: "There exists a significant body
of animal data that demonstrates goitrogenic and even carcinogenic effects
of soy products (cf., Kimura et al., 1976)." And much more....(see their
letter to their own employer, the FDA, posted at the end of the first ABC
article which includes a full exposition and a long list of published
scientific papers).

No wonder no Government wants to do proper toxicity testing on GM soy. It
could upset the whole soy multi-billion dollar apple cart, both GM and
non-GM.

For more information on the lack of safety testing on GM soy see: 
"Where is the safety testing of GM soya?"
http://www.connectotel.com/gmfood/soyarefs.html 

In the light of this evidence is it a true scientific statement to say:
"There are no adverse health effects from GM soya"...?

Certainly these scientists from the FDA have not been willing to make such a
statement in respect of normal soya - in fact they have clearly said
something very contrary.

It seems apparent that much of the detailed testing which has now been done
on normal soy (with negative results) has not been done on GM soy, and that
therefore the GM testing is not worth the paper it is written on.

To make matters worse it is now legal in the US to label any kind of soy (GM
or otherwise) as beneficial for reducing heart disease risk (see ABC story
below), but illegal to label it as genetically modified.

God Bless America - land of the "fee".

The new labelling arrangements follow a petition submitted to the FDA by the
American Soybean Association (ASA), whose corporate partners include the
following
biotechnology/agro-chemical companies - American Cyanamid, Bayer, Dow, Du
Pont, Monsanto, Novartis and Zeneca
( http://www.oilseeds.org/partners.htm ).

According to ASA President Mike Yost: "With this one change we couldn’t have
asked for a more favorable decision by FDA, one that will benefit U.S. and
world consumers as well as U.S. soybean producers." (ASA News Release
November 16, 1998 following the initial FDA approval.)

By contrast, in submitting its comments to the FDA on the new health-claim
labelling arrangements for all soy the American Dietetic Association (ADA)
warned:

"ADA assumes that both FDA and PTI have looked extensively at the literature
regarding potential safety concerns such as allergenic reactions and
possible toxicological effects of soy. While we recognize that there is
limited research in this area, we urge FDA to consider any safety and
toxicological issues prior to finalizing this rule."
http://www.eatright.org/gov/lg012599.html 

For more information on health research on soy, see:
Soy Online Service
Uncovering the truth about soy.
http://www.soyonlineservice.co.nz/ 

NATURAL LAW PARTY WESSEX 
nlpwessex@bigfoot.com  
www.btinternet.com/~nlpwessex  

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http://abcnews.go.com/onair/2020/2020_000609_soy_feature.html 

The Other Side of Soy

Scientists Concerned Over Potential Health Risks

Since last year’s FDA approval of certain soy products as good for the
heart, grocery stores have been inundated with a variety of soy-based goods.
Click on the image to watch video of the report on the controversy over
their health benefits. (ABCNEWS.com)

By Brian Ross and Richard D. Allyn

June 9 — From tofu and tacos to burgers and baby formula, soy products have
swept the nation as a healthy source of high protein, with a reputation for
being all natural and all good.
But a 20/20 investigation has found that amid all of this praise, some
scientists are now challenging this popular wisdom, and suggesting there may
be a downside to this “miracle food.”
“The safety issues are largely unanswered,” says Daniel Doerge, a
research scientist for the Food and Drug Administration and an expert on
soy.
New studies have raised questions over whether the natural ingredients
in soy might increase the risk of breast cancer in some women, affect brain
function in men and lead to hidden developmental abnormalities in infants.
This unresolved scientific debate continues to develop. Just last
October, soy enjoyed a huge boost when the FDA issued a health claim,
concluding that soy may lower both cholesterol levels and the risk of heart
disease.
But two of the FDA’s experts on soy — Doerge and his colleague, Daniel
Sheehan — have stepped forward to criticize their own agency’s claim and
even attempted in vain to stop the recommendation. Their main concern: that
the claim could be misinterpreted as a much broader endorsement for soy
protein, beyond benefits solely for the heart.
Signing a highly unusual letter of protest to their employer, Doerge
and Sheehan pointed to research that demonstrates a link between soy and
fertility problems in certain animals. (You can find a copy of the letter in
the related stories section on the right-hand column.) [posted at bottom of
this message - NLPWessex]
“The animal data is a clear indication for adverse effects, the
potential for adverse effects in humans,” Doerge says to 20/20.

Debate Over Soy Infant Formula

The core of their concern rests with the chemical make-up of soy: in
addition to all the nutrients and protein, exists a natural chemical that
mimics estrogen, the female hormone. Some studies in animals show that this
chemical can alter sexual development. And in fact, two glasses of soy milk
a day, over the course of a month, contains enough of the chemical to change
the timing of a woman’s menstrual cycle. “We are doing a large uncontrolled
and unmonitored experiment on human infants,” Sheehan says. “We’re exposing
infants to the chemicals in soy infant formula that are known to have
adverse effects in experimental animals, and we have never looked in the
human population to see if they have adverse effects.”
The infant formula industry, along with some scientists, have blasted
this criticism of soy, calling it “scientifically unjustified claims that
could unduly frighten thousands of parents.”
Kenneth Setchell, a pediatrics professor at Children’s Hospital in
Cincinnati and a leading advocate of soy, contends that scientific studies
on soy show promise in fighting a number of diseases and that adverse
effects seen in animals do not apply to humans.
“There have been literally hundreds of thousands of infants that have
been raised on those soy formulas,” Setchell says to 20/20. “Some of those
infants would be well into their late 30s, early 40s now. And you know, I
don’t see evidence of tremendous numbers of cases where there are
abnormalities.”
The debate over soy formula for infants poses a major issue throughout
the country. Soy infant formula is an undeniable lifesaver for the 3 to 4
percent of babies who are allergic to or can not digest cow’s milk. However,
heavy marketing of soy infant formula has led to its much wider use,
extending well beyond just those infants who are allergic to 25 percent of
the entire formula market.
“My careful and considered professional opinion is that it makes more
sense not to needlessly expose your baby to these compounds,” says Dr.
Claude Hughes, director of the Women’s Health Center at Cedars-Sinai Medical
Center in Los Angeles. He adds that while breast-feeding is preferred,
mothers who don’t breast-feed should use a milk-based formula and choose soy
as a last resort.

Other Health Concerns

Aside from his concerns about soy’s health effects on infants, Hughes has
also raised potentially more serious questions about soy and breast cancer.
In some cases, soy is thought to protect against breast cancer. But some
studies now indicate, for other women, the chemicals found in soy may
enhance a widely found kind of estrogen-feeding breast cancer.
“It can speed up divisions of those cells that are already cancer cells
that depend on estrogen for their growth,” Hughes tells 20/20.
The multibillion dollar soy industry has insisted that the health
benefits of soy significantly outweigh any potential risk.
Soy — consumed in the form of tofu — may have a connection to
accelerated aging in the brain, according to a three decade-long study begun
by the National Institutes of Health.
Dr. Lon White of NIH says that he found greater brain aging and
shrinkage among elderly men — all Japanese-American and living in Hawaii —
who had eaten tofu at least twice a week during middle age.
“Their brains, looking at them in terms of how their brain functions,
memory cognition, their brains seemed to be showing an exaggeration of the
usual patterns we see in aging,” White says.
The soy industry countered that White’s study only shows an association
between tofu consumption and brain aging, does not prove cause and effect
and is in conflict with research on Asian populations and animals.
While the scientific research on soy is still emerging and is often
contradictory, there are now some serious questions being raised about this
miracle food, and some of its staunchest defenders acknowledge that these
questions need to be answered.

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Posted by ABC NEWS at:
http://abcnews.go.com/onair/2020/2020_000609_soyfdaletter_feature.html 

Scientists Protest Soy Approval In Unusual Letter, FDA Experts Lay Out
Concerns

Researchers Daniel Doerge and Daniel Sheehan, two of the Food and Drug
Administration’s experts on soy, signed a letter of protest, which points to
studies that show a link between soy and health problems in certain animals.
The two say they tried in vain to stop the FDA approval of soy because it
could be misinterpreted as a broader general endorsement beyond benefits for
the heart. The text of the letter follows.

DEPARTMENT OF HEALTH
and HUMAN SERVICES
Public Health Service
Food and Drug Administration
National Center For Toxicological Research
Jefferson, Ark. 72079-9502

Daniel M. Sheehan, Ph.D.
Director, Estrogen Base Program
Division of Genetic and Reproductive Toxicology
and
Daniel R. Doerge, Ph.D.
Division of Biochemical Toxicology

February 18, 1999

Dockets Management Branch (HFA-305)
Food and Drug Administration
Rockville, MD 20852

To whom it may concern,

We are writing in reference to Docket # 98P-0683; “Food Labeling:
Health Claims; Soy Protein and Coronary Heart Disease.” We oppose this
health claim because there is abundant evidence that some of the isoflavones
found in soy, including genistein and equol, a metabolize of daidzen,
demonstrate toxicity in estrogen sensitive tissues and in the thyroid. This
is true for a number of species, including humans. Additionally, the adverse
effects in humans occur in several tissues and, apparently, by several
distinct mechanisms.

Genistein is clearly estrogenic; it possesses the chemical structural
features necessary for estrogenic activity (; Sheehan and Medlock, 1995;
Tong, et al, 1997; Miksicek, 1998) and induces estrogenic responses in
developing and adult animals and in adult humans. In rodents, equol is
estrogenic and acts as an estrogenic endocrine disruptor during development
(Medlock, et al, 1995a,b). Faber and Hughes (1993) showed alterations in LH
regulation following developmental treatment with genistein. Thus, during
pregnancy in humans, isoflavones per se could be a risk factor for abnormal
brain and reproductive tract development. Furthermore, pregnant Rhesus
monkeys fed genistein had serum estradiol levels 50- 100 percent higher than
the controls in three different areas of the maternal circulation (Harrison,
et al, 1998). Given that the Rhesus monkey is the best experimental model
for humans, and that a women’s own estrogens are a very significant risk
factor for breast cancer, it is unreasonable to approve the health claim
until complete safety studies of soy protein are conducted. Of equally grave
concern is the finding that the fetuses of genistein fed monkeys had a 70
percent higher serum estradiol level than did the controls (Harrison, et al,
1998). Development is recognized as the most sensitive life stage for
estrogen toxicity because of the indisputable evidence of a very wide
variety of frank malformations and serious functional deficits in
experimental animals and humans. In the human population, DES exposure
stands as a prime example of adverse estrogenic effects during development.
About 50 percent of the female offspring and a smaller fraction of male
offspring displayed one or more malformations in the reproductive tract, as
well as a lower prevalence (about 1 in a thousand) of malignancies. In
adults, genistein could be a risk factor for a number of estrogen-associated
diseases.

Even without the evidence of elevated serum estradiol levels in Rhesus
fetuses, potency and dose differences between DES and the soy isoflavones do
not provide any assurance that the soy protein isoflavones per se will be
without adverse effects. First, calculations, based on the literature, show
that doses of soy protein isoflavones used in clinical trials which
demonstrated estrogenic effects were as potent as low but active doses of
DES in Rhesus monkeys (Sheehan, unpublished data). Second, we have recently
shown that estradiol shows no threshold in an extremely large dose-response
experiment (Sheehan, et al, 1999), and we subsequently have found 31
dose-response curves for hormone-mimicking chemicals that also fail to show
a threshold (Sheehan, 1998a). Our conclusions are that no dose is without
risk; the extent of risk is simply a function of dose. These two features
support and extend the conclusion that it is inappropriate to allow health
claims for soy protein isolate.

Additionally, isoflavones are inhibitors of the thyroid peroxidase
which makes T3 and T4. Inhibition can be expected to generate thyroid
abnormalities, including goiter and autoimmune thyroiditis. There exists a
significant body of animal data that demonstrates goitrogenic and even
carcinogenic effects of soy products (cf., Kimura et al., 1976). Moreover,
there are significant reports of goitrogenic effects from soy consumption in
human infants (cf., Van Wyk et al., 1959; Hydovitz, 1960; Shepard et al.,
1960; Pinchers et al., 1965; Chorazy et al., 1995) and adults (McCarrison,
1933; Ishizuki, et al., 1991). Recently, we have identified genistein and
daidzein as the goitrogenic isoflavonoid components of soy and defined the
mechanisms for inhibition of thyroid peroxidase (TPO)-catalyzed thyroid
hormone synthesis in vitro (Divi et al., 1997; Divi et al., 1996). The
observed suicide inactivation of TPO by isoflavones, through covalent
binding to TPO, raises the possibility of neoantigen formation and because
anti-TPO is the principal autoantibody present in auto immune thyroid
disease. This hypothetical mechanism is consistent with the reports of Fort
et al. (1986, 1990) of a doubling of risk for autoimmune thyroiditis in
children who had received soy formulas as infants compared to infants
receiving other forms of milk.

The serum levels of isoflavones in infants receiving soy formula that
are about five times higher than in women receiving soy supplements who show
menstrual cycle disturbances, including an increased estradiol level in the
follicular phase (Setchell, et al, 1997). Assuming a dose-dependent risk, it
is unreasonable to assert that the infant findings are irrelevant to adults
who may consume smaller amounts of isoflavones. Additionally, while there is
an unambiguous biological effect on menstrual cycle length (Cassidy, et al,
1994), it is unclear whether the soy effects are beneficial or adverse.
Furthermore, we need to be concerned about transplacental passage of
isoflavones as the DES case has shown us that estrogens can pass the
placenta. No such studies have been conducted with genistein in humans or
primates. As all estrogens which have been studied carefully in human
populations are two-edged swords in humans (Sheehan and Medlock, 1995;
Sheehan, 1997), with both beneficial and adverse effects resulting from the
administration of the same estrogen, it is likely that the same
characteristic is shared by the isoflavones. The animal data is also
consistent with adverse effects in humans.

Finally, initial data fi-om a robust (7,000 men) long-term (30+ years)
prospective epidemiological study in Hawaii showed that Alzheimer’s disease
prevalence in Hawaiian men was similar to European-ancestry Americans and to
Japanese (White, et al, 1996a). In contrast, vascular dementia prevalence is
similar in Hawaii and Japan and both are higher than in European-ancestry
Americans. This suggests that common ancestry or environmental factors in
Japan and Hawaii are responsible for the higher prevalence of vascular
dementia in these locations. Subsequently, this same group showed a
significant dose-dependent risk (up to 2.4 fold) for development of vascular
dementia and brain atrophy from consumption of tofu, a soy product rich in
isoflavones (White, et al, 1996b). This finding is consistent with the
environmental causation suggested from the earlier analysis, and provides
evidence that soy (tofu) phytoestrogens causes 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 (Irvine,
1998), there is a mechanistic basis for the human findings. Given the great
difficulty in discerning the relationship between exposures and long latency
adverse effects in the human population (Sheehan, 1998b), and the potential
mechanistic explanation for the epidemiological findings, this is an
important study. 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 mechanism, and thus the results should
be interpreted in this context.

Does the Asian experience provide us with reassurance that isoflavones
are safe? A review of several examples lead to the conclusion “Given the
parallels with herbal medicines with respect to attitudes, monitoring
deficiencies, and the general difficulty of detecting toxicities with long
Iatencies, I am unconvinced that the long history of apparent safe use of
soy products can provide confidence that they are indeed without risk.”
(Sheehan, 1998b).

It should also be noted that the claim on p. 62978 that soy protein
foods are GRAS is in conflict with the recent return by CFSAN to Archer
Daniels Midland of a petition for GRAS status for soy protein because of
deficiencies in reporting adverse effects in the petition. Thus GRAS status
has not been granted. Linda Kahl can provide you with details. It would seem
appropriate for FDA to speak with a single voice regarding soy protein
isolate.

Taken together, the findings presented here are self-consistent and
demonstrate that genistein and other isoflavones can have adverse effects in
a variety of species, including humans. Animal studies are the front line in
evaluating toxicity, as they predict, with good accuracy, adverse effects in
humans. For the isoflavones, we additionally have evidence of two types of
adverse effects in humans, despite the very few studies that have addressed
this subject. While isoflavones may have beneficial effects at some ages or
circumstances, this cannot be assumed to be true at all ages. Isoflavones
are like other estrogens in that they are two-edged swords, conferring both
benefits and risk (Sheehan and Medlock, 1995; Sheehan, 1997). The health
labeling of soy protein isolate for foods needs to considered just as would
the addition of any estrogen or goitrogen to foods, which are bad ideas.

Estrogenic and goitrogenic drugs are regulated by FDA, and are taken
under a physician’s care. Patients are informed of risks, and are monitored
by their physicians for evidence of toxicity. There are no similar
safeguards in place for foods, so the public will be put at potential risk
from soy isoflavones in soy protein isolate without adequate warning and
information.

Finally, NCTR is currently conducting a long-term multigeneration study
of genistein administered in feed to rats. The analysis of the dose
range-finding studies are near-complete or complete now. As preliminary
data, which is still confidential, maybe relevant to your decision, I
suggest you contact Dr. Barry Delclos at the address on the letterhead, or
email him.

Sincerely,
Daniel M. Sheehan
Daniel R. Doerge

Enclosures
cc: Dr. Bernard Schwetz, Director, NCTR
Dr. Barry Delclos

REFERENCES
Cassidy, A, Bingham, S, and Setchell, KDR. Biological effects of soy protein
rich in isoflavones on the menstrual cycle of premenopausal women. Am. J.
Clin. Nutr. 60, 333- 340, 1994.

Chorazy, P.A., Himelhoch, S., Hopwood, N, J., Greger, N. G., and Postellon,
D.C. Persistent hypothyroidism in an infant receiving a soy formula: Case
report and review of the literature. Pediatrics 148-150, 1995.

Divi, R. L., Chang, H. C., and Doerge, D.R. Identification, characterization
and mechanisms of anti-thyroid activity of isoflavones from soybean.
Biochem. Pharrnacol. 54, 1087-1096, 1997.

Divi, R.L. and Doerge, D.R. Inhibition of thyroid peroxidase by dietary
flavonoids. Chem. Res. Toxicol. 9, 16-23, 1996.

Levy, JR, Faber, FA,Ayyash, L, and Hughes, CL. The effect of prenatal
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Fort, P., Lanes, R., Dahlem, S., Reeker, B., Weyman-Daum, M., Pugliese, M.,
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Fort, P, Moses, N., Fasano, M, Goldberg, T, and Lifshitz, F. Breast and
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Harrison, R. M.. Phillippi, P. P., and Henson, M.C. Effects of genistein on
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Hydovitz, JD, Occurrence of goiter in an infant on a soy diet. New Eng. J.
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Medlock, K.L., Branham, W. S., Sheehan, D.M. Effects of coumestrol and equol
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Pinchers, A, MacGillivray, MH, Crawford, JD, and Freeman, AG. Thyroid
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Setchell, KDR, Zimmer-Nechemias, L, Cai, J, and Heubi, JE. Exposure of
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Sheehan, D.M. Literature analysis of no-threshold dose-response curves for
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Sheehan, D.M. Herbal medicines and phytoestrogens: risklbenefit
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Sheehan, D.M. Isoflavone content of breast milk and soy formulas: Benefits
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Sheehan, D.M. and Medlock, K.L. Current issues regarding phytoestrogens.
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Sheehan, D. M., Willingham, E., Gaylor, D., Bergeron, J. M., and Crews, D.
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Shepard, TH, Pyne, GE, Kirschvink, JF, and McLean, CM. Soybean goiter. New
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Tong, W, Perkins, R, Xing, L, Welsh, WJ, and Sheehan, DM. QSAR models for
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