One of the most striking differences between a cat and a lie is that a cat has only nine lives.

–Mark Twain

urrently, in the realm of health foods and nutritional supplements, many plant hormones, called phytoestrogens, are being marketed as treatments and preventatives for age–related disorders, including osteoporosis. But the promotion of these hormonally–active “natural” substances usually employs the same faulty logic and shortsightedness which has been (and often still is) used to market estrogen–containing pharmaceuticals.

In the previous Integrated Supplements Newsletter, we saw that even estrogen itself is not quite the bone–building hormone it’s often purported to be. Knowing this, it shouldn’t come as any surprise to learn that the consumption of high amounts of plant–based estrogen–like chemicals isn’t likely to offer any meaningful benefit to bone health either. And despite the fact that these “natural” substances are marketed as safer alternatives to pharmaceutical estrogens, it seems that the toxicity of phytoestrogens can directly parallel many of the known toxicities of estrogen itself.

Estrogen and Bone – Why The Confusion?

Given the integral role of protective hormones, like progesterone, pregnenolone, and DHEA in bone building, one wonders why estrogen (and, more recently, estrogen–like food components) have been given center stage as treatments and preventatives for osteoporosis. Part of the reason is simply the fact that old myths die hard in the realm of biological science. The stubborn myth of menopause as a mere estrogen–deficiency state has led to some strange interpretations of the experimental findings regarding the role of estrogen in bone metabolism.

For example, in biological research, the ovaries of animals are often removed (in a procedure called ovariectomy) in order to mimic the hormonal changes experienced in menopause. Not surprisingly, ovariectomy leads to the rapid loss of bone density, and the development of osteoporosis in these animals. Often times, researchers simply describe ovariectomy as a way to “induce estrogen deficiency.” But after ovariectomy, as is the case in menopause, levels of progesterone are reduced even more drastically than levels of estrogen. Thinking of ovariectomy solely as a way to create an estrogen deficiency, has led many researchers to ignore the effects of the concomitant, and more severe, progesterone deficiency. This is a major omission which often makes the osteoporosis literature seem wildly contradictory and difficult to interpret.

Unlike progesterone, which serves to stimulate the production of new bone by osteoblasts, studies generally indicate that estrogen – and many similar food components and drugs commonly marketed as treatments or preventatives for osteoporosis – often simply inhibit the breakdown of bone by osteoclasts. In a limited context, inhibiting the breakdown of bone could be said to “prevent bone loss” and in the short term, this may even be able to increase bone mineral density somewhat. But, in the larger context, inhibiting the breakdown of bone may actually impair the overall bone–building cycle. If old, fragile bone isn’t removed properly, there’s simply no way for new, strong, healthy bone to be built in its place.

Of course, this important fact doesn’t stop the medical, nutraceutical, and nutritional marketing machines from touting the “bone–preserving” actions of their wares. In light of the many ways in which estrogen excess can impair bone formation and overall health, it would probably be naïve not to attribute much of the continuing pro–estrogen dogma directly to the financial interests of the industries (pharmaceutical companies, the soy industry, and more recently, the flaxseed/linseed industry) which have a vested interest in perpetuating it.

Like so many other instances in medicine and nutrition, interventions which sound reasonable to the lay public, and which are backed by voluminous research, can become very profitable if such research is continually and conveniently misinterpreted. With effective marketing, these interventions often remain profitable even after they are exposed as faulty and fraudulent when their underlying biological mechanisms become known. Oftentimes, the truly relevant research remains buried in the scientific journals for decades simply because no industry has yet developed the means to profit from it.

Perspectives on Phytoestrogens in Traditional Diets

Thanks in large part to the well–publicized early termination of the Women’s Health Initiative study in 2002, the alarming association between pharmaceutical hormone replacement therapy and increased risk of cancer and cardiovascular disease is now more openly recognized:

Article Link – The Women's Health Initiative: Death of the HRT hypothesis?

Yet, as the allure of estrogen replacement therapy has waned in recent years, the nutritional supplement industry has largely picked up where the pharmaceutical companies have left off – touting plant–based estrogen–like chemicals, called phytoestrogens, as “natural” or “safer” alternatives to estrogen–containing pharmaceuticals. The marketing behind these estrogens as “food–based” substances has lulled many consumers into thinking that these plant hormones must be at least relatively safe. But, for as much promotion as these phytoestrogens receive (and for as frighteningly widespread as they’ve become in our food supply) the existing research comes up far short of proving their effectiveness or long–term safety.

In the broadest sense, estrogenic compounds in plants, or, phytoestrogens, are almost impossible to avoid. Common items in any whole–food based diet, such as fruits, vegetables, whole grains, and even coffee and tea are sure to contain various components which could be defined as phytoestrogens.

But, exhibiting the typical selective short–sightedness of marketing propaganda, some of these phytoestrogens have been singled out and deified as major factors responsible for the reduced incidence of some diseases in certain countries. The soy estrogens, called isoflavones, are such examples. Currently, we find companies capitalizing on the mystique of Asian culture in order to promote soy products and isolated soy estrogens as “natural” remedies for menopausal symptoms, including osteoporosis.

On average, people in Asian cultures happen to consume more soy products (and thus, more isoflavones) relative to people who consume the standard Western diet. This fact, combined with the evidence that some Asian cultures exhibit lower rates of some age–related diseases than we do in the West has served as a remarkably flimsy justification for the massive promotion of isoflavone–rich soy foods and supplements throughout the world.

But we’re rarely told the full truth – that the research on soy isoflavones, and the industrial soyfoods which contain them, has been anything but consistent. There’s simply no way to predict what the actions of soy isoflavones will be in any given individual at any given dose – and there’s a significant body of research showing that soy isoflavones, when consumed in the doses often recommended, may have highly disruptive effects on various aspects of human metabolism. Yet, rather than advise caution in the use of soy products, soy marketers have capitalized on the conflicting research largely to appeal to different demographic targets. Soy’s isoflavones have been alternately marketed as “estrogens,” “weaker estrogens,” “anti–estrogens,” “aromatase–inhibitors,” and most recently, “selective estrogen response modifiers (SERMs).” This “evolving” terminology often makes people think that these chemicals are becoming better understood, but the only thing that the research shows for certain, is that phytoestrogens are hormonally active chemicals which should probably be avoided in amounts higher than those found in traditional food–based diets.

With this in mind, it’s important to gain a frame of reference with regard to how the consumption of modern soy foods can influence the levels of phytoestrogens in our body. The fact is, that levels of circulating isoflavones found in infants consuming soy–based formula; and in adults consuming things such as soy protein, soymilk, or isoflavone supplements, have been shown to be up to 10 times greater than the diet of Japanese adults consuming soy as part of a traditional diet:

Study Link – The phytoestrogen genistein induces thymic and immune changes: A human health concern?

Quote from the above study:

Total plasma levels of isoflavones and genistein in soy–fed infants range from 2.0 to 6.6 and 1.5 to 4.4 μ mol/liter, respectively, 10–fold greater than levels in Japanese adults whose diets have historically included soy…The recent popularity of dietary supplements containing either soy protein or isoflavones makes it possible for adults to ingest isoflavones doses severalfold greater than obtained with even a high–soy diet. Consumption of recommended doses of some of these products exposes adults to isoflavone levels similar to those in soy–fed infants on a per–weight basis, and plasma genistein levels in the soy–fed infant range were reported in adults ingesting commercial supplements.

Given the fact that isoflavones and other phytoestrogens are hormonally active compounds, is it reasonable to believe that an intake of isoflavones 10 times greater than the diet we’re supposedly trying to emulate will produce benefits without risks? This same question applies, not just to soy, but to supplementation with high doses of all phytoestrogens, including lignans from flaxseed, polyphenols from tea, and whichever “superfood” antioxidant extract happens to be “hot” at any given moment.

And, in the face of the soy/phytoestrogen propaganda machine, let us not forget the obvious: that the differences between the modern Westernized diet and the traditional Asian diet are so numerous, that to single out isolated components such as isoflavones as the major health–promoting factors is more than a bit of a stretch. Even after thousands of studies have examined the effects of soy foods and isoflavones added to a Western diet, only a handful could honestly be interpreted as even implying any benefit for bone health – to say nothing of their potential side effects.

Though we constantly hear about soy consumption in Asia, it’s important to realize, as well, that traditional Asian soy foods were very different than the overly–processed soymilks, soy protein isolates, and soy–based meat substitutes which are sold around the world today. It’s been well–documented that such industrial processing alters protein structures into uniquely toxic compounds. In addition, many soy–based toxins (including the isoflavones) were likely to be minimized by the fermentation processes used to prepare traditional soy dishes. It has even been noted that the fermented soy food, natto (which is almost unheard of in the West), contains particularly high levels of bacterial–formed Vitamin K. As we shall see in future Newsletters in this series, adequate intakes of Vitamin K alone could easily be responsible for dramatic improvements in bone, and cardiovascular health (benefits which are often attributed to the phytoestrogens).

As modern Asian cultures switch away from traditional soy foods, and towards the same processed variety we’re subjected to here in the US, their levels of osteoporosis are rising steadily, and are poised to be the highest in the world in the coming decades. In fact, certain markers of health in Asian cultures are probably currently being greatly over–estimated solely for marketing purposes. Although the countries of China, Japan, and Korea, do consume significantly more soy isoflavones, on average, than we do in the United States, this factor doesn’t necessarily seem to be conferring significant benefits upon bone health.

For example, although native Japanese women do have relatively low rates of hip fracture; studies have shown that their rates of vertebral fracture are even greater than those of American Caucasian women:

Study Link – Vertebral fracture prevalence in women in Hiroshima compared to Caucasians or Japanese in the US.

Quote from the above study:

The observation that, among these three populations, hip fracture incidence is lowest but spine fracture prevalence is greatest among native Japanese suggests that different risk factors may be responsible.

In essence, though phytoestrogens can be found in any whole food–based diet, and such diets are generally healthy, purposefully increasing our intake of phytoestrogens through supplements and certain phytoestrogen–rich foods isn’t likely to impart quite the health benefits we’re often promised. Instead, a high intake of isolated phytoestrogens is likely to impart negative consequences upon overall health. It shouldn’t come as any surprise that many of the negative effects of phytoestrogens mimic the negative effects of estrogen itself.

Estrogen, Phytoestrogens, and Immunity

In a significant sense, estrogen, and many foods which contain estrogen–like components are generally toxic to the immune system (that is, toxic to both circulating immune cells, and to the major regulator of immune function, the thymus gland, itself).

It just so happens that the osteoclasts which break down bone, and the osteoblasts which build bone, are immune cells. More precisely, the osteoclast is considered to be a type of macrophage – an immune cell which can engulf and break down various foreign or damaged particles (in this case, bone). Estrogen has repeatedly been shown to trigger the destruction of osteoclasts:

Study Link – Estrogen inhibits bone resorption by directly inducing apoptosis of the bone–resorbing osteoclasts.

Quote from the above study:

These data suggest that the protective effects of estrogen against postmenopausal osteoporosis are mediated in part by the direct induction of apoptosis of the bone–resorbing osteoclasts by an estrogen receptor–mediated mechanism.

And similarly, the soy estrogens, genistein and daidzein, have been shown to suppress osteoclast activity by several possible mechanisms:

Study Link – Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational, and dietary intervention studies.

Quote from the above study:

Genistein and daidzein both suppress osteoclast activity by a number of possible mechanisms, including induction of apoptosis, activation of protein tyrosine phosphatase, inhibition of cytokines, changes in intracellular Ca ++, and membrane depolarization

The fact that estrogen and phytoestrogens kill or impair the cells which break down bone can be selectively interpreted to mean that they “inhibit bone loss” but this certainly isn’t reason enough to believe that they improve overall bone health. In order to do so, a substance would have to support the building of new, strong bone. But, in fact, as evidence of the general toxicity of estrogen on immune cells, some studies have shown estrogen to inhibit the function of bone–building osteoblasts as well:

Study Link – Potential mechanism of estrogen–mediated decrease in bone formation: estrogen increases production of inhibitory insulin–like growth factor–binding protein–4.

Quote from the above study:

Thus, [estrodiol] acts on osteoblastic cells to increase availability of inhibitory IGFBP–4, by both increasing its production and decreasing its degradation, which may oppose the mitogenic effect of the IGFs on osteoblastic cells. This action may mediate, at least in part, the decreases in bone formation that are observed after estrogen treatment in vivo.

And, as further evidence of the immune–disrupting nature of various estrogens, other studies show that estrogen, the soy estrogen genistein, and the estrogen from plastic production, bisphenol A, all inhibit the production of the potent immunomodulating thymic hormone, thymosin alpha–1.

Study Link – Inhibitory effect of natural and environmental estrogens on thymic hormone production in thymus epithelial cell culture.

Quote from the above study:

The production of thymosin–alpha 1 by TECs was significantly inhibited by increasing concentrations of 17beta–estradiol (natural estrogen) over 3 x 10(–11) M, genistein (phytoestrogen) over 3 x 10(–9) M, coumestrol (phytoestrogen) over 3 x 10(–9) M, alpha–zearalanol (livestock anabolic) over 3 x 10(–7) and bisphenol–A (plastic) over 3 x 10(–6) M. Small amounts of estrogen receptor were present in the TECs. The above results clearly indicate that natural and environmental estrogens directly modulate TECs to produce thymic hormone probably through an estrogen receptor mechanism. Furthermore, our finding may be useful for evaluating biological effects of chemicals with estrogenic activity.

To give a frame of reference, the synthetic version of thymosin alpha–1 is currently used as treatment for liver disorders including several types of chronic hepatitis. Thymosin alpha–1 is also used therapeutically in other disorders characterized by disordered immune function such as some cancers and HIV/AIDS. The liver–toxic effects of estrogen are well documented (though often ignored), and estrogen’s disruptive effect on the immune system is thought to play a major role in the development of autoimmune disorders. This role of estrogen probably explains why women are more susceptible to autoimmune disorders than men.

There’s much reason to believe that, similar to endogenously–produced estrogens, an excess of phytoestrogens in the diet, (and from supplementation) will burden the liver, and produce wholesale disruption of almost every known facet of immune function as well.

In the following study, ovariectomized adult mice were administered the soy phytoestrogen, genistein, in amounts which allowed serum genistein levels to mimic those of soy–formula–fed human infants. The result was a shocking atrophy of the thymus gland (up to 80% loss), along with major thymic and immune dysfunction:

Study Link – The phytoestrogen genistein induces thymic and immune changes: a human health concern?

Quote from the above study:

Use of soy–based infant formulas and soy/isoflavone supplements has aroused concern because of potential estrogenic effects of the soy isoflavones genistein and daidzein. Here we show that s.c. genistein injections in ovariectomized adult mice produced dose–responsive decreases in thymic weight of up to 80%...Genistein injected at 8 mg/kg per day produced serum genistein levels comparable to those reported in soy–fed human infants, and this dose caused significant thymic and immune changes in mice. Critically, dietary genistein at concentrations that produced serum genistein levels substantially less than those in soy–fed infants produced marked thymic atrophy. These results raise the possibility that serum genistein concentrations found in soy–fed infants may be capable of producing thymic and immune abnormalities, as suggested by previous reports of immune impairments in soy–fed human infants.

Phytoestrogens and Hormonal Disruption

There exists a dominant belief in our culture that any product which is “natural” or which is sold over the counter must be at least reasonably safe. In actual practice, however, we must not let the often–used “natural” moniker lure us into a false sense of security or safety. Usually, very little thought is given to just how potent modern dietary supplements and nutraceuticals have become, and how drug–like their actions really are. Because many plant estrogens are marketed to support menopausal symptoms and bone health, it’s probably important to gain some meaningful perspective on their effects on hormonal balance, and their true risk–to–benefit ratio.

Rather than acting as “weak estrogens” or estrogen antagonists as their marketing often implies, phytoestrogens often exhibit some of the harmful effects of estrogen itself. The possibility certainly exists that phytoestrogens may add to the overwhelming estrogenic burden most of us (men and women) face in modern industrialized society. In essence, women turning to “natural alternatives” to avoid the side effects of estrogen should be aware that phytoestrogens may not be without similar risks of their own.

As a very practical example, the mere consumption of soy protein (even one containing a relatively low amount of isoflavones), is sufficient to significantly alter the menstrual cycle of pre–menopausal women:

Study Link – Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women.

Quote from the above study:

Soy protein (60 g containing 45 mg isoflavones) given daily for 1 mo significantly (P < 0.01) increased follicular phase length and/or delayed menstruation. Midcycle surges of luteinizing hormone and follicle–stimulating hormone were significantly suppressed during dietary intervention with soy protein. Plasma estradiol concentrations increased in the follicular phase and cholesterol concentrations decreased 9.6%. Similar responses occur with tamoxifen, an antiestrogen undergoing clinical trial as a prophylactic agent in women at high risk for breast cancer.

In the above study, soy protein ingestion led to an increased level of estradiol (a type of estrogen) and a decreased level of progesterone. It’s hard to fathom how any rational scientist could interpret these effects of soy protein as positive. The researchers who conducted the study noted that the effects of soy protein were similar to those of the “anti–estrogen” drug, tamoxifen. But tamoxifen, though sometimes used as a treatment or preventative for breast cancer, has been shown to cause a dramatic increase in liver cancer. This fact should be kept in mind, as we’ll discuss the liver toxicity of other phytoestrogens later in this article.

Studies have also shown that soy protein isolate, containing the phytoestrogen, genistein, leads to the growth of estrogen–dependent breast cancer cells when fed to mice:

Study Link – Soy Diets Containing Varying Amounts of Genistein Stimulate Growth of Estrogen–dependent (MCF–7) Tumors in a Dose–dependent Manner.

Quote from the above study:

Here we present new information that soy protein isolates containing increasing concentrations of genistein stimulate the growth of estrogen–dependent breast cancer cells in vivo in a dose–dependent manner.

And additionally, equol (produced from the soy isoflavone, daidzein) and enterolactone (produced from the phytoestrogenic lignans in flaxseed), have also been shown to stimulate the growth of breast cancer cells. Interestingly, where equol and enterolactone are produced from the bacteria in the human intestines when soy and flax are eaten, the researchers noted that these compounds could have stimulatory effects on cancer – particularly cancers of the liver and gastrointestinal tract.

Study Link – Stimulation of breast cancer cells in vitro by the environmental estrogen enterolactone and the phytoestrogen equol.

Quote from the above study:

Unexpectedly, we found that enterolactone and enterodiol, as well as equol, are weak estrogens, and that enterolactone and equol could stimulate the growth of estrogen–dependent breast cancer cell lines. We suggest that these environmental agents can promote the growth of breast cancer, particularly hormone–dependent metastases that may be located near the gut or in the mesenteries or liver, where the concentration of these intestinally produced compounds would be highest.

We previously looked at the role estrogen can play in increasing prolactin levels, and the detrimental effects prolactin can have on bone. Studies have shown that flaxseeds, which are known to contain some of the most estrogenic components of any food, increase serum prolactin levels:

Study Link – Flaxseed consumption influences endogenous hormone concentrations in postmenopausal women.

Quote from the above study:

In this group of postmenopausal women, consuming flaxseed in addition to their habitual diets influenced their endogenous hormone metabolism by decreasing serum 17 beta–estradiol and estrone sulfate and increasing serum prolactin concentrations.

Note: In the above study, although prolactin was elevated, flaxseeds reduced serum levels of the estrogens, 17 beta–estrodiol and estrone. This is probably not due to flax’s phytoestrogen content, but to its’ laxative–like effect. Anything which reduces bowel transit time can improve the excretion of estrogens and endotoxins from the gastrointestinal tract, thus taking a burden off the liver. This effect is beneficial in some respects, but the other hormonal and prolactin–elevating effects of the potent plant estrogens in flax are probably reason for us to choose safer means of staying “regular.”

And, as relates to prolactin, it’s interesting to note that the estrogenic chemical, Bisphenol A, which has received a spate of negative press recently as a toxin produced in the manufacture of plastic, has been shown to exert some of its hormone–disrupting effects by similarly increasing prolactin levels:

Study Link – The environmental estrogen bisphenol A stimulates prolactin release in vitro and in vivo.

Phytoestrogens And The Liver

Given that phytoestrogens are hormonally active chemicals which can disrupt the endocrine and immune systems, it’s not terribly surprising that our body deals with them in much the same way it would other toxins – it tries to “detoxify” them, and remove them from the body. Therefore, it’s always important to consider the effect of food–based estrogens on the body’s hormonal detoxification systems. The liver uses processes called sulfation and glucuronidation to rid the body of estrogen. Phytoestrogens are detoxified in the same fashion, and a large amount of them in the diet can often inhibit the proper metabolism of endogenous estrogens by the liver:

Study Link – Phytoestrogens Are Potent Inhibitors of Estrogen Sulfation: Implications for Breast Cancer Risk and Treatment.

Quote from the above study:

…dietary flavonoids may be able to influence the bioavailability of endogenous estrogens, and disrupt endocrine balance, by increasing the ratio of active estrogens to inactive estrogen sulfates in human tissues.

In some studies, phytoestrogens seem to “stimulate” liver function, as the detoxifying activities of the liver are ramped up in response to the toxic threat posed by these foreign, hormonally active, substances. Various researchers and phytoestrogen marketers have interpreted such studies as evidence of the beneficial effects of phytoestrogens on liver function and hormonal balance. But adding to the liver’s burden as phytoestrogens do, it’s unlikely that the long–term ingestion of these compounds (especially in high doses) will prove to be anything but toxic.

Along these lines, the scientific literature contains many reports of liver toxicity in people ingesting phytoestrogens from herb and food extracts. Even the seemingly innocuous polyphenols from green tea (which also happen to be phytoestrogens) have been linked with frighteningly severe liver damage in people taking products containing concentrated green tea extracts – including various weight loss and “diet” supplements.

And yet, we find that green tea extracts are currently being promoted for osteoporosis prevention based on epidemiological studies showing that tea drinkers often maintain a higher bone mineral density as they age:

Study Link – Epidemiological evidence of increased bone mineral density in habitual tea drinkers.

Quote from the above study:

Habitual tea consumption, especially for more than 10 years, has significant beneficial effects on BMD of the total body, lumbar spine, and hip regions in adults.

But the use of green tea extracts, in which the estrogenic polyphenols are concentrated in artificially high amounts, raises the question: can the long–tem effects of tea drinking be mimicked through the use of these high potency extracts?

When we think about it rationally, it’s probably more than a little naïve to assume that consuming the phytoestrogenic equivalent of say, 10 cups of green tea in a single herbal capsule won’t have a completely different effect on the body than consuming 10 cups of actual green tea (with all of its nutritional components) over the course of several days. Flooding the body with massive amounts of hormonally–active substances via an oral route is well–known to place a relatively severe burden on the liver, as the liver tries frantically to rid the body of these foreign hormone–like substances.

And yet, the negative effects of high–dose herbal extracts are often conveniently ignored – at the same time, we frequently hear nutritional supplements touted because they contain the “most potent herbal extracts available.” Their liver toxicity is probably a major reason why so many isolated plant components and “antioxidants” fail to live up to the initial promise shown in laboratory settings. Despite the hoopla over food and herbal extracts in recent years, many of these substances have yet to prove themselves safe or effective in any real–world environment – and in some cases they have proven to be overtly liver–toxic.

Of course, it’s always difficult to pinpoint a single cause of liver damage in any given individual, but the following report relays the story of a patient who presented with symptoms of liver injury on two separate occasions, both after having taken a green–tea–containing dietary supplement for several weeks.

Report Link – Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis).

Quote from the above report:

In our patient, the temporal pattern of C. sinensis administration and liver enzyme abnormalities (with a positive rechallenge and exclusion of other possible causes) strongly suggested that the supplement was the inciting agent for both episodes of severe, symptomatic drug–induced liver injury.

See also:

Report Link – Acute liver failure induced by green tea extracts: Case report and review of the literature.

Similarly, some studies have found disconcerting associations between the use of some herbal supplements and the occurrence of fulminant hepatic failure. Fulminant hepatic failure (FHF) is defined as the severe impairment of liver function in the absence of preexisting liver disease. Its presence is often linked to environmental factors such as drug use (including the common over–the–counter pain reliever, acetaminophen), and increasingly, herbal dietary supplements:

Study Link – High Prevalence of Potentially Hepatotoxic Herbal Supplement Use in Patients With Fulminant Hepatic Failure.

Quote from the above study:

Ten patients (50%) were recent or active users of potentially hepatotoxic supplements or herbs; 10 had no history of supplement use. In the supplement group, 7 patients (35%) had no other identified cause for hepatic failure. Six patients in the supplement group and 2 patients in the nonsupplement group underwent orthotopic liver transplantation. Five patients in each group died. There were no significant differences in transplantation rate (P = .07) or survival (P>.99) between groups. Supplement use alone accounted for the most cases of [fulminant hepatic failure] during this period, exceeding acetaminophen toxicity and viral hepatitis.

As relates to our discussion of bone health, the phytoestrogens contained in herbal extracts commonly promoted to menopausal women have also been shown to induce liver damage in a small, but not insignificant, number of individuals:

Study Link – Black cohosh and other herbal remedies associated with acute hepatitis.

Quote from the above study:

The most serious illness occurred in a 47–year–old woman who was taking black cohosh for symptoms related to the menopause. Histological examination of her explant liver confirmed severe hepatitis and multiacinar dropout.

Study Link – A Case of Acute Cholestatic Hepatitis Caused By the Seeds of Psoralea–corylifolia.

Quote from the above study:

…Boh–Gol–Zhee (in Chinese, Bu Ku Zi), appeared to be the cause for acute cholestatic hepatic injury in the following case. Psoralea corylifolia is known to contain a sufficient amount of phyto–estrogen. Some alternative medicine therapists claim that Psoralea corylifolia is effective for the treatment of osteoporosis… High concentrations of phyto–estrogen, such as genistein, have been found in the leaves of Psoralea corylifolia… The authors observed a case of acute cholestatic hepatitis in a post–menopausal woman caused by seeds of Psoralea corylifolia in amounts over 10 times the usual dose. Other possible causes of liver injury were excluded by laboratory tests and imaging studies. After discontinuation of this remedy, elevated liver enzyme and total bilirubin rapidly returned to normal.

The most important thing to realize about the potential liver–toxic effects of phytoestrogens is that these plant components invariably add to the cumulative detoxifying burden of the liver. The question of what will happen if concentrated sources of phytoestrogens are consumed along with other common liver toxins like alcohol or acetaminophen has scarcely been investigated. In the above case reports, it’s unlikely that the use of herbal supplements was the only factor in the patients’ liver disorders, but the significant risks of liver damage from phytoestrogen use in real–world situations are almost universally ignored. It’s worth noting as well, that some reports indicate that women are much more susceptible to phytoestrogen–induced liver damage than men. It seems that an excess of these substances can easily add to a women’s often already–hefty detoxifying burden.

In actual practice, the best way to reap the benefits of a healthy diet is usually to consume real foods in a manner reasonably similar to how they have been traditionally prepared. As mentioned previously, any whole–food based diet will contain phytoestrogens, but such a diet will also contain many factors which will protect us from the toxicity associated with an excess of these hormonally–active chemicals. Coffee and tea, for example, both contain phytoestrogens, but each also contains factors (e.g. caffeine, caffeic acid, chlorogenic acid, magnesium, etc.) which may be uniquely protective of liver function.

Coffee, for example, though often maligned by alternative and conventional medical practitioners alike, has been shown to impart various protective effects on liver function due to its various biologically active components:

Study Link – Unexpected effects of coffee consumption on liver enzymes.

Quote from the above study:

In coffee drinkers, liver enzymes (gamma–glutamyl transferase, alanine–amino transferase, and alkaline phosphatase) and serum bilirubin were lower than in non–coffee–drinking subjects or in those consuming less than 3 cups daily.

Study Link – Coffee consumption and the risk of primary liver cancer: Pooled analysis of two prospective studies in Japan.

Quote from the above study:

Our findings support the hypothesis that coffee consumption decreases the risk of liver cancer.

A Practical Word on Progesterone

It’s important to note as well, that it’s not only estrogen and estrogen–like chemicals which can impair liver function. Even protective hormones like progesterone, can also impair liver function if they are taken improperly or in excess. Oral natural progesterone pills (which are relatively rare) should be avoided. The dose of these pills is often very high (~200 mg) in order to account for progesterone’s destruction by the liver when taken orally. But, as we’ve seen, taxing the liver in this way is exactly what we should be trying to avoid. If progesterone is taken orally, many experts recommend a specially–prepared formulation of progesterone dissolved in natural Vitamin E oil. This preparation is said to bypass destruction by the liver, and is able to elevate progesterone levels safely, with the use of a relatively low dose.

Most commonly, progesterone is delivered in the form of skin creams found in over–the–counter preparations. These creams usually possess a high degree of safety because of the lower dose of progesterone used (~20 mg per dose), and because the transdermal route largely bypasses metabolism by the liver. The rate of absorption from these creams, however, can vary depending upon how the individual product is formulated. Creams which contain phytoestrogens in addition to progesterone should be avoided, and all hormonal intervention should be undertaken under the guidance of a qualified healthcare professional.

Phytoestrogens in Perspective

We’ve already seen how osteoporosis is, in fact, characterized by a relative estrogen excess, not an estrogen deficiency, as is commonly supposed. Knowing that maintaining the proper detoxifying function of the liver is hugely important for balancing the level of estrogen relative to the protective hormones (e.g. progesterone, pregnenolone and DHEA); it’s likely to be counterproductive to further impair liver function by consuming high dose extracts of estrogen–like chemicals from foods and herbs.

At first, it seems oddly inconsistent that the (justifiable) public outcry against estrogen–like chemicals produced as a result of industrial plastic manufacturing, hasn’t led people to abstain from ingesting high doses of similar endocrine–disrupting chemicals when they are produced by plants. But as has been well–documented time and time again, just a little well–crafted marketing is all it takes to make even very intelligent people take leave of their common sense. While phytoestrogens will almost never be problematic in truly traditional whole food based diets, the heavy promotion of the most estrogenic foods and herbs (like soy, flax, as well as herbal extracts from green tea, black cohosh, beta sitosterol, et al.), can easily lead to the over–consumption of plant–based estrogens in both men and women. Because the currently fashionable practices of supplementation and dietary manipulation may cause our intake of phytoestrogens to increase to unprecedented levels, hormonal disruption, faulty immune function, as well as liver and gastrointestinal disorders, may be more apt to result than any improvement in bone health.

Coming up Next…

Now that we know a little bit about the hormonal and environmental factors which can influence the building of bone, we’re poised to delve deeper into the nutritional factors which play a role as well. Balancing of the endocrine environment, often including low dose supplementation with protective hormones such as progesterone and DHEA should, ideally, only be undertaken in conjunction with a dietary program tailored to improving hormonal metabolism. In the next issue of the Integrated Supplements Newsletter, we’ll take a look at some of the most important nutrients, as well as some of the dietary substances which should be avoided, if our goal is to build and maintain healthy bones for a lifetime.