Moducare warning

May 14, 2002

, thank you so much for the info. I was unaware of any of that but will

totally check it out. Hope all is well

-Val

May 15, 2002

Just for the record, phyto-estrogens are perfect matches to our own estrogens

that our bodies make. I seriously doubt it is the plant-derived estrogen

that is causing cancer. Usually the estrogen that gives us problems is the

animal-derived estrogen or chemically manufactured. Hope that clears up some

confusion. God bless Colleen

>

> Message: 13

> Date: Tue, 14 May 2002 19:32:23 -0000

> From: " jessered57 " <jessered57@...>

> Subject: Moducare warning

>

> Dear Val,

>

> I did some more checking into Moducare and it's Beta-Sitosterols.

> Beta-Sitosterols are a phyto-estrogen (plant-estrogen) and some

> researchers are saying that they may be harmful. They may crowd the

> estrogen receptors and block real estrogen. They are also questioning

> wheater it may actually cause cancer. So until the controversy is

> cleared up you may want to stay away from this stuff. Just perform a

> search on the web for Beta-Sitosterol & immune.

>

> > Hey just curious has anyone heard of a supplement called moducare.

> I heard it was supposed to be great for fibro and other diseases

> becasue it lowers cortisol levels. Any info would be much

> appreciated. thanks -Val

May 15, 2002

It may be safe, I really don't know but here is what I based the

warning on. Beta-sitosterol is one of the isoflavones and phyto-

estrogens and is classified the same as genistien and equol.

Coincidently Soybeans also contain high levels of beta-sitosterols.

There are some wonderful claims made about it and some benefits shown

in clinical studies but as pointed out, it is a two-edged sword.

There are also warnings like this one:

Scientists Protest Soy Approval

In Unusual Letter, FDA Experts Lay Out Concerns

Researchers Doerge and 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

M. Sheehan, Ph.D.

Director, Estrogen Base Program

Division of Genetic and Reproductive Toxicology

and

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,.

Faber and (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 (on, 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 (on, 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 s 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. 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,

M. Sheehan

R. Doerge

> > > Hey just curious has anyone heard of a supplement called

moducare.

> > I heard it was supposed to be great for fibro and other diseases

> > becasue it lowers cortisol levels. Any info would be much

> > appreciated. thanks -Val

>

May 15, 2002

Jessie, thank you so much for that interseting article I could not find any

information on the subject. I have been thinking about taking moducare but maby

not a good idea. Have you ever heard of another product called Sea Silver? this

is another product on the internet a lot and a lot of people are talking about

it. Just wondering if you had heard of it. thanks again hope all is well. -Val

May 16, 2002

Dear Val,

Another question that looks easy, but.................

I guess the " claim to fame " for Sea Silver is Colloidal Silver but it

also has Pau D " Arco, Aloe Vera, Cranberry and 10 sea weeds. I haven't

tried the Colloidal Silver so I can't say anything bad or good about

it. There is still one problem though. People think of Herbals like

they do about vitamins but they couldn't be farther from the truth. A

plant is a chemical factory and most of these chemicals have an

effect on our bodies. Some of them have powerful antibiotic/

antiviral properties but they also affect our hormones and immune

system. The chinese would never think of gathering a group of herbs

and say that they were right for most diseases and most importantly

every person. They always prescribed per each individual. In modern

times it shouldn't be any different. Each of us has a different

genetic makeup and will react differently to each herb. I have one

base herb that I am taking and I am slowly adding others. Generally I

will add a new one at night before I lay down to see if my muscle

twitches comes back or any other problems develop. But before I add

anything I check to make sure it doesn't counteract a specific

antibiotic or any other medicine I may be taking. Go to www.gnc.com

and do a search on each Herb and look at the health notes. These will

tell you of any possible side effects or drug interactions. Don't be

perturbed. If you want, you can get Colloidal Silver at GNC for about

$10 and then try adding some other stuff like the Pau D'Arco

gradually so that you will know if anything is bad for you. Generally

it is going to take a minimum of 30 to 60 days to notice a benefit,

but fortunately bad effects come right away and you can stop. I know

it sounds stupid and you have probably heard it before but listen to

what your body is telling you. I went to ginger because I kept having

a craving for dumb Ginger Snap Cookies, but even they didn't stop the

craving until I started eating the candied ginger.

Good Luck

> Jessie, thank you so much for that interseting article I could not

find any information on the subject. I have been thinking about

taking moducare but maby not a good idea. Have you ever heard of

another product called Sea Silver? this is another product on the

internet a lot and a lot of people are talking about it. Just

wondering if you had heard of it. thanks again hope all is well. -Val

May 16, 2002

, Thak you again for the info. I agree these herbs can really effect a lot

of other things and everybody is different. The sea silver claims to have a

phytosilver in it which is different from the collodial silver. I dont kow what

is it though. I have used collodial silver in the past froma company called CS

pro and i think it did help. I might try to look up all the things in sea silver

to get more information. Thank you again hope all is well-Val

May 18, 2002

>snip plant is a chemical factory

, you are very wise, grasshopper! you have snatched pebble from

masters hand.

really very good advice.

roe

[ ] Re: Moducare warning