Originally posted by: akodi
natenut, it's a myth, there are actually 3 types of phytoestrogens that can be consumed and in this case of soy the type is isoflavone which decreases risk of osteoporosis, breat cancer, and uterus cancer. this is mainly important for women that are looking to avoid estrogen spikes due to menopause, don't worry about the man boobage eat as much soy as you life, it won't kill ya, plus it's good if you're working out cause pumping so much Fe will take a toll on your bones. good luck
here we go:
As many of you know, soy contains "healthy" amounts of compounds known as phytoestrogens, which are simply plant chemicals that mimic the action of animal estrogen. (For the purposes of this article, the term "estrogen" is intended as a generic term for any substance that exerts biological effects characteristic of estrogenic hormones such as estradiol.)
Now, phytoestrogens can affect mammalian cells in two ways that I know of?they can either bind to high-affinity, highly specific receptors in the cell nucleus which, in turn, attach to DNA regions of genes that lead to protein transcription, in effect acting as a real estrogen, or they can simply bind to these receptor sites and sit there, preventing real estrogen from getting its parking space and initiating transcription.
The first possible effect is highly undesirable if you're a male because estrogen, in addition to being the primary "female" hormone and responsible for a host of "feminizing" effects, also, in greatly simplified terms, makes it harder to put on muscle.
Now, it could be argued that yes, these phytoestrogens act as estrogen, but very weak estrogen. So if they prevent a "strong" estrogen from setting up shop on the receptor, you're ahead of the game. That's a good point, unless you have a low level of estrogen in the first place, which would mean that the weak activity of the weak estrogen itself can exceed whatever estrogen activity is being blocked, leading to a net increase.
The second possible effect can be a good one. If an inert substance, like a "friendly" phytochemical, prevents estrogen from binding to a receptor site and initiating protein transcription, you miss out on all of the negative effects of estrogen (possible increases in bodyfat, gynecomastia, and maybe even benign prostatic hypertrophy, or BPH).
Unfortunately, soy protein contains two rather significant "unfriendly" phytoestrogens, both of which appear to have estrogenic activity. They are called genistein and diadzein.
I maintain that male physique athletes?or, for that matter, virtually all males?should avoid taking in large amounts of soy protein on a regular basis. This holds true for school-age kids, too.
Obviously, the government has made it a lot more likely that the US population, including prepubescent and adolescent males, is going to be eating fairly significant amounts of soy protein. What will be the results of this "soy mania?"
I can't be sure?any more than the Y2K experts were sure of what would happen on January 1?but it could be increased feminization of our school-age children, increased feminization of our male adults and all the baggage that carries, and possibly even increased rates of infertility and an even more universal increase in BPH.
Am I a Chicken Little, or is there genuine cause for concern? The studies seem to back me up. Some point to the hint of estrogenic activity, while others point to more serious problems.
One in particular, using mice, found genistein (2.5 mg/kg of bodyweight for nine days) to result in reduced testicular and serum testosterone concentrations, in addition to a reduced amount of luteinizing hormone in the pituitary.(1) They concluded that genistein, when given to adult males, "induced typical estrogenic effects in doses comparable to those present in soy-based diets."
Another found that a soy and alfalfa-free diet with a 0.1% concentration of genistein decreased the rate of bodyweight gain in Sprague-Dawley rats and a marginal decrease in prostate weight.(2) (Although avoiding prostate hypertrophy is a good thing in adults, a decrease in prostate weight is indicative of feminizing effects.) The scientists concluded that scientists who do endocrine toxicology studies should use phytoestrogen-free diets, lest the phytoestrogens interact with manmade chemicals and screw up the results.
Others found more serious problems. One cited "significant testicular cell death" when genistein was administered.(3) They noted that while sodium azide, a highly toxic chemical that's a potent vasodilator, killed testicular cells by inducing necrotic death, genistein killed them by inducing apoptoic death (in essence, fragmentation of the cells)?a small distinction, in my book. This sperm death may be a result of their inability to repair themselves. (4)
Much of the research is geared toward reproductive disorders in wild animals, captive animals, and the animal known as man. One study suggests that developmental and reproductive disorders in wild animals have been associated with a high exposure to environmental chemicals that also have estrogenic activity.(5) He conducted experiments in which he exposed rat endometrial cells to various compounds, including genistein and diadzein, and found them to indeed affect a certain protein that affected fertility.
Although Hopert's study pegged females, part of the reproductive problems might very well stem from the affects of phytoestrogens on the male, as the above studies suggest.
Similarly, a study of cheetahs in captive breeding programs, most of which ingest a commercial diet that includes hefty amounts of soy, suffered from infertility and a high incidence of liver disease. (6) The incidence of liver disease is, perhaps, the topic of another article.
There's been documented decline in human male sperm count in the last 50 years, and various theories have been bandied about as to its cause. Many scientists believe that it coincides with an increase in exposure to estrogen-like compounds. Although soy hasn't typically been a major component of diets in the western world, that may be about to change.
It's true that the Japanese and Chinese have long ingested soy and soy products and, quite obviously, they don't appear to suffer from infertility. Of course, they're probably not exposed to the incredible variety of environmental estrogens prevalent in the western world. All of the chemicals that we face each day, combined with the added burden of phytoestrogens from soy, might be enough to push us over the edge.
However, if I can get "unscientific" for a moment, practically everyone would agree that it's rare to see a particularly muscular Asian. Could the blame be ascribed to genetic factors, a difference in training methodologies, a difference in cultural priorities or, at least partly, a diet based on soy protein? I certainly don't know.
I don't know what the repercussions of the government's newly found love of soy will be, either. Will it lead to increased infertility? A society of young men who are more female than male? A lack of vigor that's indicative of reduced levels of testosterone?
Furthermore, I don't know the repercussions of the fitness industry's newfound love of soy. Will using soy proteins make it harder to put on muscle?
Again, I don't know. I certainly think that more research needs to be done before soy, like another evil of Pandora's nutritional box, is set loose upon the world.
I do know that I won't use soy protein powders or eat any soy products other than an occasional bowl of Miso soup. Furthermore, I know that I won't give my dog any dog foods that contain soy and, if I had children, I'd pack their lunch.
References
1) Strauss, et al. "Genistein exerts estrogen-like effects in male mouse reproductive tract," Mol Cell Endocrinol 1998 Sep 25;144(1-2);83-93
2) Casanova M, et al. "Developmental effects of dietary phytoestrogens in Sprague-Dawley rats and interactions of genistein and diadzein with rat estrogen receptors alpha and beta in vitro," Toxicol Sci 1999 Oct;51(2):236-44
3) Kumi-Diaka J, et al. "Cytotoxic potential of the phytochemical genistein isoflavone and certain environmental chemical compounds on testicular cells," Biol Cell, 1999 Sep;91 (7): 515-23
4) Anderson, et al. "Effect of various genotoxins and reproductive toxins in human lymphocytes and sperm in Comet assay," Teratog Carcinog Mutagen 1997;17(1);29-43
5) Hopert, et al. "Characterization of estrogenicity of phytoestrogens in an endometrial-derived experimental model," Environ Health Perspect 1998 Sep;106(9); 581-6
6) Setchell, et al. "Dietary Estrogens?a probable cause of infertility and liver disease in captive cheetahs," Gasteroenterology 1987 Aug;93(2);225-33
OH BUT THERE'S MORE!
Two of America's Most Wanted
Unfortunately, the two soy isoflavones that I mentioned previously can have numerous adverse effects on everything ranging from Testosterone production, thyroid production, muscle growth, and even health.
Let's consider soy's affects on T production first. The ability of soy protein to decrease Testosterone levels has been well demonstrated. One study displayed a 76% reduction of Testosterone production in men, after ingestion of soy protein over a brief period of time.(4) In yet another study, an inverse association was found between soy protein intake and Testosterone levels in Japanese men.(5)
Finally, in yet another study, using healthy adult males, a diet containing soy was compared to a diet that consisted of meat protein in terms of sex hormone concentrations. Well, after evaluation, Testosterone levels were significantly lower in the soy diet. Not only this, but the estimated amount of free Testosterone was 7% lower after the soy diet as well.(6)
Hey, mice didn't fare much better. Testosterone and LH were also lowered in mice consuming only the isoflavone genistein.(7)
The evidence seems pretty conclusive. There may, of course, be other factors, but it's enough to give one pause when considering whether or not he should add some soy to his next protein drink.
IGF, Thyroid, and the Girly Hormones
It's fairly clear that soy protein lowers testosterone levels. How does it affect estrogen and progesterone levels? You'd figure that genistein would at least reduce the activity of estrogen to some extent, since it binds at the same receptor site, right? Well, apparently not. It turns out that genistein does not inhibit the effects of estradiol and in fact has been demonstrated to exert an additive effect when combined with estradiol.(2,8)
This means that they don't interfere with one another and can both exert the same negative effects at the same time, thus, packing a double punch. Furthermore, genistein may potentially increase estradiol levels as well. It's thought that this may occur because genistein may deconjugate estrone in the gut and allow for it to reabsorb into the bloostream and convert to estradiol.(9)
It's possible that it may also exert some progestational activity.(10) Even worse is that the estrogenic activity of these phytoestrogens may have been underestimated in the past, as there is evidence that they may be much more potent in vivo as opposed to in vitro [test tube] studies.(11) Oh, and while we're still on the topic or hormones, soy protein has also been shown to decrease IGF-1 concentrations in male rats.(12) Oh, and I'd feel bad if I forgot to mention that it can lower T4 levels, too.(13)
Protecting Our Future
While planting a seed definitely isn't an immediate goal of mine, I'm sure there are plenty of guys out there who wish to pass on their superior genes. So, for these men, I urge you to not let your child or pregnant wife consume any products that contain soy. While there isn't concrete evidence as of yet, there's still enough to warrant some caution.
For instance, when female rats were fed genistein while pregnant, their pups weighed significantly less than the groups that weren't fed genistein.(14) Also, when young rats were given genistein, spermatogenesis decreased, as did body weight, testicle size, and possibly the urge to mate. Another study found similar results.(15,16)
Oh, and before I forget, genistein has been shown to cause testicular cells to die, in vitro at least.(17)
Healthy? I Think Not
The main reason why the government decided to "sponsor" soy protein was because it can supposedly reduce the risk of heart disease. However, the funny, or scary, thing is that soy has actually been shown to decrease HDL cholesterol.(18,19) HDL cholesterol is the good kind.
Furthermore, it's possible that the isoflavones can induce growth and malignancy of the prostate. This is because the ER Alpha is thought to be at least partially responsible for the induction of growth. So, in theory, since genistein can agonize the ER Alpha in much the same way as estradiol, then it could cause growth of the prostate.(20)
Okay, So What About my Muscles?
Okay, now let's move on to the important stuff. How good is soy protein in terms of increasing muscle growth? Well, when compared to casein, it was beaten in terms of both protein synthesis and breakdown.(21) So, we know that it can't match proteins like casein or whey. What else? Well, even though this might make you cringe, I feel obligated to tell you. Get this, genistein was shown to inhibit myoblast proliferation and fusion in a dose-dependent manner!
It decreased protein synthesis and inhibited protein accretion as a result. These results occurred even at the lowest dose. The authors concluded that if animals consume enough soy, those concentrations of genistein could potentially affect normal muscle growth and development.(22)
Now that's some frightening stuff! Okay, so things couldn't get any worse for soy, right? Well not only may it interfere with muscle growth, but it may screw with your pro-hormone usage. Why is that? Well, genistein may interfere with the conversion of 4-androstenediol to Testosterone, thus, reducing the effectiveness of your favorite supplement to a good degree! This happens because it interferes with the enzyme 3 Beta-HSD.(23)
The End?
Boy, I wish it were the end, but the fact is that many companies, with the encouragement of the government, will continue to add soy protein to their products. However, like many of us fringe-element weight lifters have for so many years, we'll stand by and endure while the rest of the world makes a big mistake.
The next thing you know, there will be a big story about how truly harmful this stuff is to the male. Hopefully it won't be too late. But hey, maybe I'm being a bit hypercritical here. I mean, who knows, this may actually be a good supplement for the average woman. They seem to think they need more estrogen and less muscle, so more power to 'em.
For those T-Vixens, however, stay away from it! Especially while pregnant. Anyhow, my advice for you would be to read every food and supplement label that you have to make sure that there isn't any soy within the product. I mean, hey, you'll be checking the macronutrient profile anyhow, so just skim on down to the ingredients from now on. Be careful, you'd be surprised by how many items have been tainted. For now, good luck and keep your eyes peeled.
References Cited
1.Breinholt V, et al. "Estrogenic activity of flavonoids in mice. The importance of estrogen receptor distribution, metabolism and bioavailability." Food Chem Toxicol 2000 Jul;38(7):555-64
2.Casanova M, et al. "Developmental effects of dietary phytoestrogens in Sprague-Dawley rats and interactions of genistein and daidzein with rat estrogen receptors alpha and beta in vitro." Toxicol Sci 1999 Oct;51(2):236-44
3.Stahl S, et al. "Phytoestrogens act as estrogen agonists in an estrogen-responsive pituitary cell line." Toxicol Appl Pharmacol 1998 Sep;152(1):41-8
4.Zhong, et al. "Effects of dietary supplement of soy protein isolate and low fat diet on prostate cancer." FASEB J 2000;14(4):a531.11
5.Nagata C, et al. "Inverse association of soy product intake with serum androgen and estrogen concentrations in Japanese men." Nutr Cancer 2000;36(1):14-8.
6.Habito RC, et al. "Effects of replacing meat with soyabean in the diet on sex hormone concentrations in healthy adult males." Br J Nutr 2000 Oct;84(4):557-63
7.Strauss L, et al. "Genistein exerts estrogen-like effects in male mouse reproductive tract." Mol Cell Endocrinol 1998 Sep 25;144(1-2):83-93
8.Santell RC, et al. "Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic/pituitary axis in rats." J Nutr 1997 Feb;127(2):263-9
9.Harrison RM, et al. "Effect of genistein on steroid hormone production in the pregnant rhesus monkey." Proc Soc Exp Biol Med 1999 Oct;222(1):78-84
10.Zand RS, et al. "Steroid hormone activity of flavonoids and related compounds." Breast Cancer Res Treat 2000 Jul;62(1):35-49
11.Nagel SC, et al. "The effective free fraction of estradiol and xenoestrogens in human serum measured by whole cell uptake assays: physiology of delivery modifies estrogenic activity." Proc Soc Exp Biol Med 1998 Mar;217(3):300-9
12.Aukema HM, Housini I. "Dietary soy protein effects on disease and IGF-1 in male and female Han:SPDR-cy rats." Kidney Int 2001 Jan;59(1):52-61
13.Klein M, et al. "Energy metabolism and thyroid hormone levels of growing rats in response to different dietary proteins?soy or casein." Arch Tierernahr 2000;53(2):99-125.
14.Flynn KM, et al. "Effects of genistein exposure on sexually dimorphic behaviors in rats." Toxicol Sci 2000 Jun;55(2):311-9
15.Atanassova N, et al. "Comparative effects of neonatal exposure of male rats to potent and weak (environmental) estrogens on spermatogenesis at puberty and the relationship to adult testis size and fertility: evidence for stimulatory effects of low estrogen levels." Endocrinology 2000 Oct;141(10):3898-907
16.Whitten PL, et al. "Phytoestrogen influences on the development of behavior and gonadotropin function." Proc Soc Exp Biol Med 1995 Jan;208(1):82-6
17.Kumi-Diaka J, et al. "Cytotoxic potential of the phytochemical genistein isoflavone (4',5',7-trihydroxyisoflavone) and certain environmental chemical compounds on testicular cells." Biol Cell 1999 Sep;91(7):515-23
18.Ashton E, Ball M. "Effects of soy as tofu vs meat on lipoprotein concentrations." Eur J Clin Nutr 2000 Jan;54(1):14-9
19.Madani S, et al. "Dietary protein level and origin (casein and highly purified soybean protein) affect hepatic storage, plasma lipid transport, and antioxidative defense status in the rat." Nutrition 2000 May;16(5):368-75.
20.Risbridger G, et al. "Evidence that epithelial and mesenchymal estrogen receptor-alpha mediates effects of estrogen on prostatic epithelium." Dev Biol 2001 Jan 15;229(2):432-442
21.Schadereit R, et al. "Whole body protein turnover of growing rats in response to different dietary proteins?soy protein or casein." Arch Tierernahr 1999;52(4):311-21
22.Ji S, et al. "Soybean isoflavones, genistein and genistin, inhibit rat myoblast proliferation, fusion and myotube protein synthesis." J Nutr 1999 Jul;129(7):1291-7
23.Keung WM. "Dietary estrogenic isoflavones are potent inhibitors of beta-hydroxysteroid dehydrogenase of P. testosteronii." Biochem Biophys Res Commun 1995 Oct 24;215(3):1137-44
NOT DONE YET!
There's a lot of talk today about soy. Turn on the news and its soy, read a diet book and you'll find soy, go to your local gym and a personal trainer will recommend soy. What is it about soy that has captivated this nation? Well for starters it has many health benefits backed up by good science, it's inexpensive, it has a good track record in Asia, and the government has allowed a seal of approval to be stamped on food items that contain 6.25 grams of soy protein.
Sounds like soy is a "can't miss" product, but is it? In this article we'll uncover the darker side of supposedly innocent soy and show you why you might not choose to include it in your otherwise healthy diet.
Many papers have exhorted the benefits of soy, but as the saying goes "if it sounds too good to be true, it probably is" fits soy better than anything else you might imagine.
Science has shown soy, more importantly its phyto-estrogen components, namely genistein, has the ability to attach to estrogen receptor sites and through transcription, act as female hormones such as estradiol. This, in some cases, can have benefits so it's not strange that soy would receive some well-deserved attention. The problem with this attention is that individuals who have no need of soy, and even some to which soy could be hazardous, have started using it. Science is now beginning to see what this "benign" protein can do, though.
This review will cover the negative effects that soy protein may have on fetal development of both males and females, hormonal balance in males of a pre-mature and mature age, and efforts of weight training individuals trying to increase fat-free muscle mass. Studies will be included of human and non-human species, both immature and mature in age. Only abstracts and full-length articles from peer reviewed journals will be referenced in this paper.
Literature
Both abstracts and journals were found through the PubMed database and in the local university library. Limits were set on searches such as "human only," "male," "female," "abstract only," and others. Key words used included "soy," "soy protein," "genistein," as well as "Testosterone production," "effects on Testosterone," and others. Finally, studies or points in favor of soy were not included, as countless papers have been written on its positive effects.
Findings
The largest concern scientists have about soy are its effects on sexual development of infants consuming soy-based formula. The data is startling, yet most concerns have fallen on deaf ears.
One study showed that when manufacturer-suggested amounts of soy formula are fed to infants, the infants ingest a daily dose of approximately 3 mg of total isoflavones (i.e. genistein and daidzein) per kg of body weight, which is maintained at a fairly constant level between 0 and 4 months of age.(3) Supplementing the diet of 4-month old infants with a single daily serving of soy-based cereal can increase their isoflavone intake by over 25%, depending on the brand chosen.
This rate of isoflavone intake is much greater than that shown to alter reproductive hormones in adult humans. The available evidence suggests that infants can digest and absorb dietary phytoestrogens in active forms and neonates are generally more susceptible than adults to perturbations of the sex-steroid milieu.
Another study assessed the effect of administering neonatal animals genistein in the amount of 4 mg per kg per day from days 2-18 of life.(1) Administration of genistein significantly retarded most measures of pubertal spermatogenesis. Plasma FSH levels in the treatment groups changed in parallel to the spermatogenic changes (reduced when pubertal spermatogenesis retarded, increased when pubertal spermatoenesis advanced).
By day 25, the changes in FSH levels largely persisted. In adulthood, the animals that were fed a soy-free diet in infancy and on, had significantly larger testes than controls fed a soy-containing diet. Of the animals that had neonatal treatment with genistein, a minority did not mate or were infertile.
In concluding this article, the authors stated "the presence or absence of soy or genistein in the diet has significant short-term (pubertal spermatogenesis) and long-term (body weight, testis size, FSH levels, and possibly mating) effects on males."
The ugliness continues. The developing fetus is uniquely sensitive to perturbation with estrogenic chemicals. The carcinogenic effect of prenatal exposure to diethylstilbestrol (DES) is the classic example. The carcinogenic potential of genistein, a naturally occurring plant estrogen in soy, has been shown in mice treated neonatally. In a study reported in the journal, Cancer Research, the incidence of uterine adenocarcinoma in 18-month-old mice was 35% for genistein and 31% for DES (diethylstilbestrol).(6)
This data suggests that genistein is carcinogenic if exposure occurs during critical periods of differentiation. The author admonished: "Thus, the use of soy-based infant formulas in the absence of medical necessity and the marketing of soy products designed to appeal to children should be closely examined."
Finally, as far as soy and its effects on infants, hypothyroidism has been shown in infants receiving soy formula.(2)
The next major concern is genistein's estrogenic and anti-androgenic effects on adult male animals and humans. This effect was shown clearly in a study on adult male reproductive tracts.(8) In intact adult male mice, genistein (2.5 mg per kg of body weight per day for only 9 days) reduced testicular and serum Testosterone concentrations and pituitary LH-content. These results suggest that genistein ? in doses comparble to those that would exist in a soy-based diet ? induced typical estrogenic effects.
A second study showed plasma Testosterone and androstenedione levels were significantly lower in the animals fed a phytoestrogen-rich diet compared with animals fed a phytoestrogen-free diet.(9) These results indicated that consumption of dietary phytoestrogens over a relatively short period can significantly alter plasma androgen hormone levels.
In a study of Japanese men, total and free Testosterone concentrations were inversely correlated with soy product intake. (5)
The evidence continues. In rats that were fed a diet in which casein was replaced by soy protein isolate/isoflavones, both serum levels of Testosterone and weight of testes were significantly reduced.(7)
Finally, in a study that may correlate more strongly with weight-training athletes, diets that consist of inferior protein (soy) may increase protein breakdown in skeletal muscle.(4) Pigs were fed diets based on soybean-protein isolate or casein for 15 weeks. A transient rise in the level of cortisol was shown to occur in the postprandial phase only in the soybean group. The authors of this study concluded: "These data suggest that the inferior quality of dietary soybean protein induces hormonally-mediated upregulation of muscle protein breakdown for recruitment of circulatory amino acids in a postabsorptive state."
In other words, soy intake induces the body to break down muscle protein in order for it to get its required amino acids.
Conclusions
At this time it's recommended that:
? Infants not be given soy-based formula until more research is done on safety in regard to neonatal sexual development and its effects on thyroid suppression.
? Men not use soy products until more research is done on its effects on Testosterone and testicular function.
? Weight-training individuals who hope for increased muscle hypertrophy not use soy protein until more research is done on effects of decreased Testosterone, increased cortisol levels and muscle protein breakdown.
Scientists Protest Soy Approval in Unusual Letter
Scientists' Letter
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 this 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. Additi