Soy Isoflavones, Panacea or Poison?

[Guest guest]

<http://www.westonaprice.org/soy/isoflavones.html>

 

Soy Isoflavones, Panacea or Poison?

by Mike Fitzpatrick, PhD, MNZIC

 

The following article was submitted to the FDA in an effort to block inclusion

of estrogen-like compounds called isoflavones, found in large amounts in soy

products, in the GRAS (Generally Recognized as Safe) list of ingredients in

foods and medicines.

 

Introduction

 

The Archer Daniels Midland Company (ADM) have provided the Food and Drug

Administration (FDA) with notice that it has determined that the substance soy

isoflavone is generally recognised as safe (GRAS). This notice was made in

accordance with the FDA proposed rule 'Substances Generally Recognized as Safe'

21 CFR Parts 170, 184, 186 and 570. In support of this notice, ADM have provided

a document entitled " An information document reviewing the safety of soy

isoflavones used in specific dietary applications. "

 

In my opinion soy isoflavone (or more correctly, the soy isoflavones) should not

be granted GRAS status. In fact given the current state of knowledge in the body

of scientific literature it would make more sense, in terms of risk assessment,

to prohibit the addition of soy isoflavones to foods. Further, manufacturers

should act to minimise the exposure of the human and animal population to these

compounds that appear to occur in all foods that contain soy protein. This

opinion is based on my understanding of the scientific literature on soy

isoflavones and some experience as a researcher in the field.

 

Soy Isoflavones: History of Use

 

In order to prove the GRAS status of soy isoflavones it is critical for ADM to

demonstrate that soy isoflavones have enjoyed a long and safe history of use.

Hence ADM claim that 'these isoflavone components...have been consumed by

millions of humans for over two thousand years'. However, their claim is not

based on fact and neither is there any evidence provided to substantiate their

claim.

 

The claim that isoflavones have been consumed for thousands of years has become

quite common in isoflavone scientific literature, however it is no more than an

assumption and appears based on the general perception that historical soybean

consumption was widespread in Asia.

 

Although soybean products have been consumed in some parts of Asia for many

hundreds of years (1) they did not form a significant part of the diet (2).

Also, the traditional soybean was quite different to the soybean as we know it

today.

 

Glycine soja , the wild soybean, is found in northern, north-eastern and central

China, adjacent areas of the former USSR, Korea, Taiwan and Japan. Glycine soja

is the species of soybean that was consumed traditionally and is the ancestor of

the modern cultivar, Glycine max (3).

 

The isoflavone content of Glycine max was first reported about 60 years ago (4)

but it is impossible to know with certainty whether Glycine soja contained

isoflavones. It is well established that Glycine max is, compositionally, quite

different to Glycine soja . For example, Glycine max contains approximately

21.0% oil compared with 9.8% in Glycine soja and Glycine max also contains more

protein (3). This is quite expected because Glycine max has been cultivated to

have maximised economic potential.

 

It has also been shown that plants such as that as Glycine max produce

phytoestrogens such as the soy isoflavones as a defence mechanism in response to

pests (5). Increased disease resistance has been a consistent goal of soybean

breeders and it is quite conceivable that this goal has served to increase the

levels of isoflavones, and other naturally occurring toxins, in Glycine max .

 

It is also well established that different cultivars of Glycine max can contain

widely variable levels of isoflavones (6). If this is so then it is not

implausible that the traditional Asian soybean, Glycine soja , contained quite

low levels of isoflavones, or perhaps none at all.

 

Therefore, a counter argument to the ADM claim of long and safe use could be

that isoflavones have entered the human food chain only in relatively recent

times. It has been the cultivation of Glycine max coupled with mass production

technology and incorporation of soy protein into numerous foods that has

resulted in these compounds being almost unavoidable in the human diet. This

mass exposure has only occurred in the last 30 years and it is still

undetermined whether isoflavones are safe or not.

 

In summary, ADM cannot show a long and safe history of use because there is no

evidence to substantiate their claim 'that isoflavones have been consumed by

millions of humans for over two thousand years'.

 

Soy Isoflavones: Safety of Use

 

ADM claim 'a long safe history of consumption for soy products and soy foods'.

The issue of the safety of soy products in relation to isoflavone toxicity and

risk:benefit considerations has been the subject of a recently published paper

(7) by a senior scientist at the FDA National Center for Toxicological Research

(NCTR), Dr Daniel Sheehan. Sheehan is 'unconvinced that the long history of

apparent safe use of soy products can provide confidence that they are indeed

without risk' and likens soy products to herbal medicines stating that the

'confidence that soy products are safe is clearly based more on belief than hard

data'.

 

Even if ADM'S claims in relation to soy isoflavones, 'no toxic effects at normal

dietary levels', were correct (which they are not, see Section 4) this does not

provide evidence that soy products are safe. This is because the potential

harmful effects of soy isoflavones have never been thoroughly investigated.

 

There have been several studies that attempt to define the acute toxicity of soy

isoflavones in various experimental animals and these are cited in the ADM

document.

 

However, the prime concern in relation to estrogenic compounds such as the soy

isoflavones is the potential for chronic endocrine system and reproductive

toxicity and alterations to the immune system (8,9). As such the harmful effects

of soy isoflavones would not have been obvious if they did exist. A compelling

example is the estrogenic drug, diethylstilbestrol (DES). Treatment with DES

continued for over 20 years before physicians fortuitously made the association

between its use and the incidence of a rare type of malignancy in DES daughters

(10). In the case of soy isoflavones, however, the fact that estrogenic

compounds are present in soy foods has not been general knowledge to health

professionals until quite recently. Therefore, any link between effect and cause

is unlikely to have been made.

 

Until more extensive epidemiological studies are undertaken with clearly

identified endpoints (such as breast cancer, thyroid disease or immune system

dysfunction) it must be concluded that there is no certainty that soy

isoflavones are safe at all.

 

Soy Isoflavones: Adverse Effects

 

ADM argue that 'these isoflavone components...have been consumed by millions of

humans for over two thousand years with no recorded adverse effects'.

Furthermore ADM claim that 'published epidemiology and feeding studies in both

animals and humans indicate no toxic effects at normal dietary levels' and that

'soy isoflavones, as part of a soybean based diet, are not associated with

reports of adverse health effects'.

 

It is difficult to reconcile these statements with published scientific

literature which is replete with reports of adverse effects and toxicity of

isoflavones at dietary levels. In fact it was the toxicity of dietary levels of

isoflavones to animals that first raised the awareness of the scientific

community to the fact that soy isoflavones were endocrine disrupters (11).

 

Reproductive effects, infertility, thyroid disease or liver disease due to

dietary intake of isoflavones had been observed for several animals including

cheetah (12), quail (13), mice (14), rats (15), sturgeon (16) and sheep (17).

 

With regard to sheep toxicity ADM claim that the 'adverse effects were

attributed to feeding on subterranean clover and are associated with coumestrol

and the isoflavone formononetin'. This is another example of misinformation in

the ADM document. In fact it is generally accepted that sheep metabolise

formononetin to the soy isoflavone daidzein. Daidzein is, in turn, metabolised

to equol which is believed to be responsible for the type of infertility

referred to as 'clover disease' (18). There can be no doubt that if sheep were

fed a diet supplemented with soy isoflavones they would, depending on dose and

duration, develop clover disease.

 

In another study it has also been reported that 9 out of 20 young calves died

when fed a soybean milk replacer (19). The authors implicated 'phenolic

compounds' as the reason of increased prostaglandin synthesis, gastrointestinal

disorders, tachycardia, bronchoconstriction and death. Soy isoflavones have the

potential to interfere with normal prostaglandin synthesis and are, therefore, a

likely explanation for this toxicity in calves. It should be noted that in a

control group of calves fed an ethanol extracted soybean milk replacer, only 4

out of 20 deaths occurred. Ethanol extraction reduced the amount of phenolics,

which would have included isoflavones, in the soybean milk replacer 2.18% to

1.00%.

 

ADM claim that 'infertility effects are not general to all animals ' citing work

by Lundh (20). However, this author does not even investigate inter-species

differences in reproductive toxicity due to isoflavones. Rather, his work shows

how different species metabolise isoflavones differently. Although not all

animals become infertile after consuming soy isoflavones at normal dietary

levels for restricted periods, feeding at such levels does result in profound

endocrine effects in all animals species studied to date.

 

ADM also claim that 'soy isoflavones have been widely consumed and are

recognised to be non-toxic' citing Petrakis et al. (21) and Setchell et al.

(22). In fact, nowhere in either of these papers do the authors state that soy

isoflavones are recognised as non-toxic.

 

Petrakis et al. found that consumption of soy protein has a stimulatory effect

on the pre-menopausal breast. Although Setchell et al. state that 'there is no

evidence to suggest that ingestion of isoflavones...has adverse effects in human

beings', they acknowledge 'the potential effect that these bioactive compounds

may produce...is unknown'.

 

It is incorrect to state that there is no evidence of harmful effects of soy

isoflavones on humans. In fact there is mounting evidence that dietary levels of

soy isoflavones cause thyroid disease and may increase the risk of breast

cancer.

 

Goitre and hypothyroidism were reported in infants fed soybean diets until the

early 1960's (23). In fact recent reports indicate that thyroid disorders may be

attributable to feeding soy-based infant formulas (24-25). Further, a study on

37 adults showed that diffuse goitre and hypothyroidism appeared in half of the

subjects after consuming 30 g per day of pickled roasted soybeans for three

months (26). These findings are consistent with the recently proposed mechanism

by which soy isoflavones affect thyroid hormone synthesis (27).

 

It is concluded that soy isoflavones can be the cause of thyroid disorders in

soy consumers and, hence, there is every indication that cases of goitre and

hypothyroidism in infants were caused by the soy isoflavones. Unless diets that

include soy isoflavones are adequately supplemented with iodine, goitre will

result. In this regard Kay et al. discuss the minimum safety iodine requirement

for a soybean diet (28).

 

However, even if iodine supplementation does occur, under conditions of high

chronic doses of isoflavones persistent inhibition of thyroid hormone synthesis

could potentially lead to thyroid cancer (27).

 

With regard to breast cancer, Dees et al. have shown that dietary concentrations

of genistein may stimulate breast cells to enter the cell cycle; this finding

led these authors to conclude that women should not consume soy products to

prevent breast cancer (29). This work is consistent with an earlier report by

Petrakis et al. who expressed concern that women fed soy protein isolate have an

increased incidence of epithelial hyperplasia (21).

 

There is no doubt that soy isoflavones are biologically active in humans. The

first report of a definitive experiment which showed this involved the

consumption of 60g of soy protein per day for one month by pre-menopausal women

(30). The soy isoflavones disrupted the menstrual cycle during, and for up to

three months after, administration. With regard to this study the ADM document

claims 'no adverse effects were noted' but the authors of the original paper did

not state this. It is appreciated that there are varying opinions in the

scientific community as to what constitutes toxicity. In recent times, however,

there has evolved a greater understanding of endocrine disrupters and their

effects. Many now view the multiplicity of effects that endocrine disrupters can

induce as toxic effects (8).

 

The inclusion of endocrine disrupters in human diets should not be taken

lightly. With specific reference to soy-based infant formulas the high soy

isoflavone intake of this population group has led Dr Sheehan to note that

infants fed soy-based formulas have been placed at risk in a 'large,

uncontrolled, and basically unmonitored human infant experiment' (31). If soy

isoflavones are granted GRAS status this experiment would spread to the greater

population and millions would be exposed to compounds which are increasingly

being shown to have adverse effects.

 

Also, the synergistic effects that soy isoflavones may induce when combined with

other xenoestrogens that the human population are exposed are beyond the scope

of this document. However, there is a general thesis that because of the

potential for synergistic effects, human exposure to all endocrine disrupters,

such as the soy isoflavones, requires urgent reduction (8).

 

Soy Isoflavones: Benefits

In recent times there have been numerous claims that isoflavones prevent hormone

related diseases such as breast cancer. Under some conditions genistein has been

found to inhibit breast cancer cell growth (32). However, there is no consensus

amongst scientists that isoflavone ingestion reduces breast cancer risk.

 

Recently the UK government published a definitive review assessing the effects

of phytoestrogens in the human diet (33). This study found that there was almost

no evidence linking health benefits from foods containing isoflavones to the

isoflavones themselves.

 

Similarly in their review of phytoestrogens and western diseases, Adlercruetz

and Mazur assert that any benefits from soy products are not due to isoflavones

specifically. They conclude that the combination of a high phytoestrogen intake

with a western diet may not be beneficial (34).

 

ADM state that 'epidemiological studies between Western and Far Eastern

populations suggest that components of soybeans may contribute to important

health effects'. However an epidemiological study in China has shown that high

soy intake is not protective against breast cancer (35).

 

Based on evidence to date it is concluded that there is little evidence for the

beneficial effects of soy isoflavones. Indeed authorities in the field do not

support the ADM thesis that soy isoflavones 'provide positive health maintenance

benefits'.

 

Summary and Conclusions

In conclusion, the recognition by the Archer Daniels Midland Company that soy

isoflavones are generally recognised as safe (GRAS) is seriously flawed. The

supporting document entitled 'An information document reviewing the safety of

soy isoflavones used in specific dietary applications' contains factual errors,

misrepresents cited authors and does not present the full body of current

scientific evidence. The conclusions reached in the ADM document are not based

on fact:

 

There is no evidence of a long and safe history of use or that 'these isoflavone

components...have been consumed by millions of humans for over two thousand

years'.

 

It is not correct that 'published epidemiology and feeding studies in both

animals and humans indicate no toxic effects at normal dietary levels' or that

'soy isoflavones, as part of a soybean based diet, are not associated with

reports of adverse health effects'.

 

Benefits of dietary intake soy isoflavones have not been proven. To the

consumer, dietary soy isoflavones represent a clear risk whereas the benefits

are highly questionable. Rather than accept that soy isoflavones are GRAS, it is

my opinion that regulatory agencies such as the FDA should give full attention

to consumer protection and deny GRAS status to soy isoflavones.

 

<http://www.westonaprice.org/soy/isoflavones.html>

--

Neil Jensen: neil

The WWW VL: Sumeria http://www.sumeria.net/

" The welfare of humanity is always the alibi of tyrants. "

-- Albert Camus