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      <H1><!-- #BeginEditable "Headline" --><B><FONT face=3DVerdana=20
      color=3D#000000>Scientists Protest Soy Approval<FONT=20
      size=3D4></FONT></FONT></B><!-- #EndEditable --></H1></TD></TR>
  <TR>
    <TD class=3DmTdContentBody>&nbsp;</TD></TR>
  <TR>
    <TD class=3DmTdContentBody><!-- #BeginEditable "Body" -->
      <P><FONT size=3D2><B>Read <A=20
      href=3D"http://www.mercola.com/2001/jun/30/soy_comments.htm">The =
Natural Law=20
      Party's comments</A> on this letter.</B></FONT></P>
      <P><FONT face=3DArial size=3D4><B><FONT color=3D#ff0033>In Unusual =
Letter, FDA=20
      Experts Lay Out Concerns </FONT></B></FONT><FONT =
face=3DArial></FONT></P>
      <P><FONT face=3DArial>Researchers Daniel Doerge and Daniel =
Sheehan, two of=20
      the Food and Drug Administration's experts on soy, <B><FONT =
color=3D#000000=20
      size=3D4>signed a letter of protest,</FONT></B> which points to =
studies that=20
      show a <B><FONT color=3D#0000cc><FONT size=3D4>link between soy =
and health=20
      problems</FONT></FONT></B> in certain animals. The two say they =
tried in=20
      vain to stop the FDA approval of soy because it could be =
misinterpreted as=20
      a broader general endorsement beyond benefits for the heart. The =
text of=20
      the letter follows.<BR><BR>Department of Health and Human=20
      Services<BR>Public Health Service<BR>Food and Drug=20
      Administration<BR>National Center For Toxicological =
Research<BR>Jefferson,=20
      Ark. 72079-9502</FONT></P>
      <P><FONT face=3DArial>Daniel M. Sheehan, Ph.D.<BR>Director, =
Estrogen Base=20
      Program<BR>Division of Genetic and Reproductive =
Toxicology<BR></FONT></P>
      <P><FONT face=3DArial>and Daniel R. Doerge, Ph.D.<BR>Division of =
Biochemical=20
      Toxicology</FONT></P>
      <P><FONT face=3DArial>Dockets Management Branch (HFA-305)<BR>Food =
and Drug=20
      Administration<BR>Rockville, MD 20852</FONT></P>
      <P><FONT face=3DArial>To whom it may concern,<BR><BR>We are =
writing in=20
      reference to <A =
href=3D"http://vm.cfsan.fda.gov/~lrd/fr991026.html">Docket #=20
      98P-0683; "Food Labeling: Health Claims; Soy Protein and Coronary =
Heart=20
      Disease.</A>" <B><FONT color=3D#000000 size=3D4>We</FONT></B> =
<B><FONT=20
      color=3D#000000 size=3D4>oppose this health claim</FONT></B> =
because there is=20
      abundant evidence that some of the isoflavones found in soy, =
including=20
      genistein and equol, a metabolize of daidzen, demonstrate toxicity =
in=20
      estrogen sensitive tissues and in the thyroid. </FONT></P>
      <P><FONT face=3DArial>This is true for a number of species, =
including=20
      humans. Additionally, the adverse effects in humans occur in =
several=20
      tissues and, apparently, by several distinct =
mechanisms.</FONT></P>
      <P><FONT face=3DArial>Genistein is clearly estrogenic; it =
possesses the=20
      chemical structural features necessary for estrogenic activity (; =
Sheehan=20
      and Medlock, 1995; Tong, et al, 1997; Miksicek, 1998) and induces=20
      estrogenic responses in developing and adult animals and in adult =
humans.=20
      </FONT></P>
      <P><FONT face=3DArial>In rodents, equol is estrogenic and acts as =
an=20
      estrogenic endocrine disruptor during development (Medlock, et al, =

      1995a,b). Faber and Hughes (1993) showed alterations in LH =
regulation=20
      following developmental treatment with genistein. </FONT></P>
      <P><FONT face=3DArial><B><FONT color=3D#0000cc size=3D4>Thus, =
during pregnancy=20
      in humans, isoflavones per se could be a risk factor for abnormal =
brain=20
      and reproductive tract development. </FONT></B></FONT></P>
      <P><FONT face=3DArial>Furthermore, pregnant Rhesus monkeys fed =
genistein had=20
      serum estradiol levels 50- 100 percent higher than the controls in =
three=20
      different areas of the maternal circulation (Harrison, et al, =
1998). Given=20
      that the Rhesus monkey is the best experimental model for humans, =
and that=20
      a women's own estrogens are a very significant risk factor for =
breast=20
      cancer, <B><FONT color=3D#0000cc size=3D4>it is unreasonable to =
approve the=20
      health claim until complete safety studies of soy protein are =
conducted.=20
      </FONT></B></FONT></P>
      <P><FONT face=3DArial>Of equally grave concern is the finding that =
the=20
      fetuses of genistein fed monkeys had a 70 percent higher serum =
estradiol=20
      level than did the controls (Harrison, et al, 1998). Development =
is=20
      recognized as the most sensitive life stage for estrogen toxicity =
because=20
      of the indisputable evidence of a very wide variety of frank =
malformations=20
      and serious functional deficits in experimental animals and =
humans.=20
      </FONT></P>
      <P><FONT face=3DArial>In the human population, DES exposure stands =
as a=20
      prime example of adverse estrogenic effects during development. =
About 50=20
      percent of the female offspring and a smaller fraction of male =
offspring=20
      displayed one or more malformations in the reproductive tract, as =
well as=20
      a lower prevalence (about 1 in a thousand) of malignancies. In =
adults,=20
      genistein could be a risk factor for a number of =
estrogen-associated=20
      diseases.</FONT></P>
      <P><FONT face=3DArial>Even without the evidence of elevated serum =
estradiol=20
      levels in Rhesus fetuses, potency and dose differences between DES =
and=20
      <B><FONT color=3D#0000cc><FONT size=3D4>the soy isoflavones do not =
provide any=20
      assurance that the soy protein isoflavones per se will be without =
adverse=20
      effects.</FONT></FONT></B> </FONT></P>
      <P><FONT face=3DArial>First, calculations, based on the =
literature, show=20
      that doses of soy protein isoflavones used in clinical trials =
which=20
      demonstrated estrogenic effects were as potent as low but active =
doses of=20
      DES in Rhesus monkeys (Sheehan, unpublished data). </FONT></P>
      <P><FONT face=3DArial>Second, we have recently shown that =
estradiol shows no=20
      threshold in an extremely large dose-response experiment (Sheehan, =
et al,=20
      1999), and we subsequently have found 31 dose-response curves for=20
      hormone-mimicking chemicals that also fail to show a threshold =
(Sheehan,=20
      1998a). </FONT></P>
      <P><FONT face=3DArial>Our conclusions are that <B><FONT =
color=3D#0000cc=20
      size=3D4>no dose is without risk;</FONT></B> the extent of risk is =
simply a=20
      function of dose. These two features support and extend the =
conclusion=20
      that it is inappropriate to allow health claims for soy protein=20
      isolate.</FONT></P>
      <P><FONT face=3DArial>Additionally, isoflavones are inhibitors of =
the=20
      thyroid peroxidase which makes T3 and T4. Inhibition can be =
expected to=20
      generate thyroid abnormalities, including goiter and autoimmune=20
      thyroiditis. There exists a significant body of animal data that=20
      demonstrates goitrogenic and even carcinogenic effects of soy =
products=20
      (cf., Kimura et al., 1976). </FONT></P>
      <P><FONT face=3DArial>Moreover, there are significant reports of =
goitrogenic=20
      effects from soy consumption in human infants (cf., Van Wyk et =
al., 1959;=20
      Hydovitz, 1960; Shepard et al., 1960; Pinchers et al., 1965; =
Chorazy et=20
      al., 1995) and adults (McCarrison, 1933; Ishizuki, et al., 1991).=20
      </FONT></P>
      <P><FONT face=3DArial>Recently, we have identified genistein and =
daidzein as=20
      the goitrogenic isoflavonoid components of soy and defined the =
mechanisms=20
      for inhibition of thyroid peroxidase (TPO)-catalyzed thyroid =
hormone=20
      synthesis in vitro (Divi et al., 1997; Divi et al., 1996). =
</FONT></P>
      <P><FONT face=3DArial>The observed suicide inactivation of TPO by=20
      isoflavones, through covalent binding to TPO, raises the =
possibility of=20
      neoantigen formation and because anti-TPO is the principal =
autoantibody=20
      present in auto immune thyroid disease. This hypothetical =
mechanism is=20
      consistent with the reports of Fort et al. (1986, 1990) of =
<B><FONT=20
      color=3D#0000cc size=3D4>a doubling of risk for autoimmune =
thyroiditis in=20
      children who had received soy formulas as infants</FONT></B> =
compared to=20
      infants receiving other forms of milk.</FONT></P>
      <P><FONT face=3DArial>The serum levels of isoflavones in infants =
receiving=20
      soy formula that are about five times higher than in women =
receiving soy=20
      supplements who show menstrual cycle disturbances, including an =
increased=20
      estradiol level in the follicular phase (Setchell, et al, 1997). =
Assuming=20
      a dose-dependent risk, it is unreasonable to assert that the =
infant=20
      findings are irrelevant to adults who may consume smaller amounts =
of=20
      isoflavones. </FONT></P>
      <P><FONT face=3DArial>Additionally, while there is an unambiguous =
biological=20
      effect on menstrual cycle length (Cassidy, et al, 1994), it is =
unclear=20
      whether the soy effects are beneficial or adverse. Furthermore, we =
need to=20
      be concerned about transplacental passage of isoflavones as the =
DES case=20
      has shown us that estrogens can pass the placenta. No such studies =
have=20
      been conducted with genistein in humans or primates. </FONT></P>
      <P><FONT face=3DArial>As all estrogens which have been studied =
carefully in=20
      human populations are two-edged swords in humans (Sheehan and =
Medlock,=20
      1995; Sheehan, 1997), with both beneficial and adverse effects =
resulting=20
      from the administration of the same estrogen, it is likely that =
the same=20
      characteristic is shared by the isoflavones. The animal data is =
also=20
      consistent with adverse effects in humans.</FONT></P>
      <P><FONT face=3DArial>Finally, initial data from a robust (7,000 =
men)=20
      long-term (30+ years) prospective epidemiological study in Hawaii =
showed=20
      that Alzheimer's disease prevalence in Hawaiian men was similar to =

      European-ancestry Americans and to Japanese (White, et al, 1996a). =
In=20
      contrast, vascular dementia prevalence is similar in Hawaii and =
Japan and=20
      both are higher than in European-ancestry Americans. </FONT></P>
      <P><FONT face=3DArial>This suggests that common ancestry or =
environmental=20
      factors in Japan and Hawaii are responsible for the higher =
prevalence of=20
      vascular dementia in these locations. Subsequently, <B><FONT =
color=3D#0000cc=20
      size=3D4>this same group showed a significant dose-dependent risk =
(up to 2.4=20
      fold) for development of vascular dementia and brain atrophy from=20
      consumption of tofu, a soy product rich in isoflavones</FONT></B> =
(White,=20
      et al, 1996b). </FONT></P>
      <P><FONT face=3DArial>This finding is consistent with the =
environmental=20
      causation suggested from the earlier analysis, and provides =
evidence that=20
      soy (tofu) phytoestrogens causes vascular dementia. </FONT></P>
      <P><FONT face=3DArial>Given that estrogens are important for =
maintenance of=20
      brain function in women; that the male brain contains aromatase, =
the=20
      enzyme that converts testosterone to estradiol; and that =
isoflavones=20
      inhibit this enzymatic activity (Irvine, 1998), there is a =
mechanistic=20
      basis for the human findings. Given the great difficulty in =
discerning the=20
      relationship between exposures and long latency adverse effects in =
the=20
      human population (Sheehan, 1998b), and the potential mechanistic=20
      explanation for the epidemiological findings, this is an important =
study.=20
      </FONT></P>
      <P><FONT face=3DArial>It is one of the more robust, well-designed=20
      prospective epidemiological studies generally available. We rarely =
have=20
      such power in human studies, as well as a potential mechanism, and =
thus=20
      the results should be interpreted in this context.</FONT></P>
      <P><FONT face=3DArial>Does the Asian experience provide us with =
reassurance=20
      that isoflavones are safe? A review of several examples lead to =
the=20
      conclusion "Given the parallels with herbal medicines with respect =
to=20
      attitudes, monitoring deficiencies, and the general difficulty of=20
      detecting toxicities with long latencies, <B><FONT color=3D#0000cc =
size=3D4>I=20
      am unconvinced that the long history of apparent safe use of soy =
products=20
      can provide confidence that they are indeed without =
risk."</FONT></B>=20
      (Sheehan, 1998b).</FONT></P>
      <P><FONT face=3DArial>It should also be noted that the claim on p. =
62978=20
      that soy protein foods are GRAS is in conflict with the recent =
return by=20
      CFSAN to Archer Daniels Midland of a petition for GRAS status for =
soy=20
      protein because of deficiencies in reporting adverse effects in =
the=20
      petition. Thus GRAS status has not been granted. Linda Kahl can =
provide=20
      you with details. It would seem appropriate for FDA to speak with =
a single=20
      voice regarding soy protein isolate.</FONT></P>
      <P><FONT face=3DArial>Taken together, the findings presented here =
are=20
      self-consistent and demonstrate that genistein and other =
isoflavones can=20
      have adverse effects in a variety of species, including humans. =
Animal=20
      studies are the front line in evaluating toxicity, as they =
predict, with=20
      good accuracy, adverse effects in humans. </FONT></P>
      <P><FONT face=3DArial>For the isoflavones, we additionally have =
evidence of=20
      two types of adverse effects in humans, despite the very few =
studies that=20
      have addressed this subject. While isoflavones may have beneficial =
effects=20
      at some ages or circumstances, this cannot be assumed to be true =
at all=20
      ages. </FONT></P>
      <P><FONT face=3DArial>Isoflavones are like other estrogens in that =
they are=20
      two-edged swords, conferring both benefits and risk (Sheehan and =
Medlock,=20
      1995; Sheehan, 1997). The health labeling of soy protein isolate =
for foods=20
      needs to considered just as would the addition of any estrogen or=20
      goitrogen to foods, which are bad ideas.</FONT></P>
      <P><FONT face=3DArial>Estrogenic and goitrogenic drugs are =
regulated by FDA,=20
      and are taken under a physician's care. Patients are informed of =
risks,=20
      and are monitored by their physicians for evidence of toxicity. =
There are=20
      no similar safeguards in place for foods, so the public will be =
put at=20
      potential risk from soy isoflavones in soy protein isolate without =

      adequate warning and information.</FONT></P>
      <P><FONT face=3DArial>Sincerely,<BR>Daniel M. Sheehan<BR>Daniel R. =

      Doerge</FONT></P>
      <P><FONT face=3DArial><A=20
      =
href=3D"http://abcnews.go.com/onair/2020/2020_000609_soyfdaletter_feature=
.html"><FONT=20
      size=3D4><B>ABC News.com</B></FONT></A> </FONT></P>
      <HR>

      <P><FONT size=3D4><B>Dr. Mercola's Comment:</B></FONT></P>
      <P><FONT face=3DArial><B>Many thanks to Valerie at <A=20
      =
href=3D"http://www.soyonlineservice.co.nz/">http://www.soyonlineservice.c=
o.nz/</A>=20
      for forwarding me the above document.</B></FONT></P>
      <P><B><FONT face=3DArial>When even the FDA's own researchers bring =
up=20
      concerns about soy, it clearly warrants a more serious evaluation. =
Drs.=20
      Sheehan and Doerge do an excellent job of summarizing some of the =
main=20
      concerns with soy.</FONT></B></P>
      <UL>
        <LI><B><FONT face=3DArial>Potential adverse effects of =
isoflavones'=20
        estrogenic influence<BR></FONT></B>
        <LI><B><FONT face=3DArial>Isoflavone inhibition of aromatase, =
the enzyme=20
        that normally produces estrogen from testosterone in both men =
and=20
        women<BR></FONT></B>
        <LI><B><FONT face=3DArial>Soy phytoestrogen's linkage to =
vascular dementia=20
        (Alzheimer's)</FONT></B>=20
        <LI><B><FONT face=3DArial>Isoflavone inhibition of thyroid =
function and=20
        increased risk of autoimmune thyroid problems<BR></FONT></B>
        <LI><B><FONT face=3DArial>Potential increase of breast cancer =
due to soy's=20
        estrogen effect</FONT></B> </LI></UL>
      <P><B><FONT face=3DArial>I recently became aware of a <A=20
      href=3D"http://www.soyonlineservice.co.nz/testimonies.htm">soy =
negative=20
      influence on thyroid testimonials page</A> that you may want to =
review.=20
      </FONT></B></P>
      <P><B><FONT face=3DArial>There are of course many other reasons =
why you will=20
      want to seriously consider limiting or avoiding soy. If this area =
is of=20
      concern to you please review the links below.</FONT></B></P>
      <P><B><FONT size=3D+0>Please also be sure to read the <A=20
      =
href=3D"http://www.mercola.com/2001/jun/30/soy_comments.htm">excellent=20
      comment</A> on the above letter by the <A=20
      href=3D"http://www.natural-law.org/">Natural Law Party</A>. =
</FONT></B><FONT=20
      face=3DArial><B><BR></B></FONT></P>
      <P><FONT face=3DVerdana><B><FONT color=3D#f00000 size=3D4>Related=20
      Articles:</FONT></B></FONT></P>
      <BLOCKQUOTE>
        <P><A href=3D"http://www.mercola.com/article/soy/"><FONT =
face=3DArial>Soy=20
        Index </FONT></A></P>
        <P><A =
href=3D"http://www.mercola.com/2000/aug/20/soy_dangers.htm"><FONT=20
        face=3DArial>Soy May Cause Cancer and Brain Damage=20
      </FONT></A></P></BLOCKQUOTE>
      <P><B><FONT face=3DVerdana size=3D2>References</FONT></B></P>
      <P><FONT face=3DVerdana size=3D2>Cassidy, A, Bingham, S, and =
Setchell, KDR.=20
      Biological effects of soy protein rich in isoflavones on the =
menstrual=20
      cycle of premenopausal women. Am. J. Clin. Nutr. 60, 333- 340,=20
      1994.</FONT></P>
      <P><FONT face=3DVerdana size=3D2>Chorazy, P.A., Himelhoch, S., =
Hopwood, N, J.,=20
      Greger, N. G., and Postellon, D.C. Persistent hypothyroidism in an =
infant=20
      receiving a soy formula: Case report and review of the literature. =

      Pediatrics 148-150, 1995.</FONT></P>
      <P><FONT face=3DVerdana size=3D2>Divi, R. L., Chang, H. C., and =
Doerge, D.R.=20
      Identification, characterization and mechanisms of anti-thyroid =
activity=20
      of isoflavones from soybean. Biochem. Pharrnacol. 54, 1087-1096,=20
      1997.</FONT></P>
      <P><FONT face=3DVerdana size=3D2>Divi, R.L. and Doerge, D.R. =
Inhibition of=20
      thyroid peroxidase by dietary flavonoids. Chem. Res. Toxicol. 9, =
16-23,=20
      1996.</FONT></P>
      <P><FONT face=3DVerdana size=3D2>Levy, JR, Faber, FA,Ayyash, L, =
and Hughes,=20
      CL. The effect of prenatal exposure to phytoestrogen genistein on =
sexual=20
      differentiation in rats. Proc. Sot. Exp. Biol. Med. 208, 60-66,=20
      1995.</FONT></P>
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}
.blogdescription {
	FONT-SIZE: 12px; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif
}
.searchResults {
	FONT-SIZE: 12px; FONT-FAMILY: Verdana, Arial, Helvetica, sans-serif
}
.standardInput {
	WIDTH: 150px; BACKGROUND-COLOR: #ffffa0
}
#StoryCnt A {
	FONT-SIZE: 14px
}
#StoryCnt A:visited {
	FONT-SIZE: 14px
}
#NewsCnt A {
	FONT-SIZE: 14px
}
#NewsCnt A:visited {
	FONT-SIZE: 14px
}
.on {
	BACKGROUND-POSITION: left top; DISPLAY: block; FONT-WEIGHT: bold; =
FONT-SIZE: 13px; FLOAT: left; BACKGROUND-IMAGE: =
url(/images/topstories_on.gif); MARGIN: 0px; WIDTH: 122px; COLOR: =
#33337e; LINE-HEIGHT: 36px; BACKGROUND-REPEAT: no-repeat; HEIGHT: 36px; =
TEXT-DECORATION: none
}
.on A {
	COLOR: #000000; TEXT-DECORATION: none
}
.off {
	BACKGROUND-POSITION: left top; DISPLAY: block; FONT-WEIGHT: bold; =
FONT-SIZE: 13px; FLOAT: left; BACKGROUND-IMAGE: =
url(/images/topstories_off.gif); MARGIN: 0px; WIDTH: 122px; COLOR: =
#b8b8b8; LINE-HEIGHT: 36px; BACKGROUND-REPEAT: no-repeat; HEIGHT: 36px; =
TEXT-DECORATION: none
}
#container A {
	FONT-SIZE: 14px; COLOR: #0b3ac1; TEXT-DECORATION: underline
}
#container A:hover {
	FONT-SIZE: 14px; COLOR: #0b3ac1; TEXT-DECORATION: none
}
.StoryCntOn {
	DISPLAY: block
}
.StoryCntOff {
	DISPLAY: none
}
.NewsCntOff {
	DISPLAY: none
}
.NewsCntOn {
	DISPLAY: block
}
.OffersCntOff {
	DISPLAY: none
}
.OffersCntOn {
	DISPLAY: block
}

------=_NextPart_000_0033_01C87B92.803DBAF0
Content-Type: application/octet-stream
Content-Transfer-Encoding: 7bit
Content-Location: http://www.mercola.com/Scripts/DefaultButtons.js


function SearchSubmit(baseURL, searchCtl)
{
    location.href = baseURL + "&Search_Keywords=" + searchCtl.value ; 
}

function DefaultButton(anEvent, btn)
{ 
	if (document.all)
	{ 
		if (event.keyCode == 13)
		{ 
			event.returnValue=false; 
			event.cancel = true; 
			btn.click(); 
		} 
	}
	else if (document.getElementById)
	{ 
		if (anEvent.which == 13)
		{ 
			anEvent.returnValue=false; 
			anEvent.preventDefault();
			btn.click(anEvent); 
		}
	}
	else if(document.layers)
	{ 
		if(event.which == 13)
		{ 
			event.returnValue=false; 
			event.cancel = true; 
			btn.click(); 
		}
	}
}
------=_NextPart_000_0033_01C87B92.803DBAF0
Content-Type: application/octet-stream
Content-Transfer-Encoding: quoted-printable
Content-Location: http://www.mercola.com/Scripts/GenericFormSupport.js

function SubmitForm(genericFormNumber)
{
	//currently this only sets the action and method of the form.  it could =
be updated to set the other=20
	//attributes if necessary.  all fields on user form need to be 'gform' =
+ genericFormNumber which ensures=20
	//we only grab values specific to the form being submitted. =09

	var sourceForm =3D document.forms["routerForm"];
	var destForm =3D document.forms["genericForm"];
	var destFormCounter =3D 0;
	var formID =3D 'gform' + genericFormNumber;
	for(var i =3D 0;i<sourceForm.elements.length;i++)
	{
		if(sourceForm.elements[i].name =3D=3D formID + '_FormAction')
		{
			destForm.action =3D sourceForm.elements[i].value;
		}
		else if(sourceForm.elements[i].name =3D=3D formID + '_FormMethod')
		{
			destForm.method =3D sourceForm.elements[i].value;
		}=09
		else if(sourceForm.elements[i].name !=3D '__ViewState' && =
sourceForm.elements[i].name.indexOf(formID + '_') =3D=3D 0)
		{=09
			var oField =3D document.createElement("input");
		=09
			oField.setAttribute("name", =
sourceForm.elements[i].name.substring(sourceForm.elements[i].name.indexOf=
('_') + 1));
			oField.setAttribute("value", sourceForm.elements[i].value);
			oField.setAttribute("type",sourceForm.elements[i].type);
			oField.setAttribute("id", sourceForm.elements[i].id);
		=09
			destForm.appendChild(oField);
		}					=09
	}
	destForm.submit();
}

function Login()
{

}
------=_NextPart_000_0033_01C87B92.803DBAF0--

