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Phytoestrogens Re-Examined

by Kate Neil(more info)

listed in nutrition, originally published in issue 65 - June 2001

Phytoestrogens are defined as the family of plant compounds, which are structurally similar to the mammalian oestrogen-oestradiol and can mimic the action of steroidal oestrogens in the body.

Flavonoids are the dominant phytoestrogen in the human diet with 4,000 different flavonoids having been identified. They are divided into seven sub-families: flavones, isoflavones, flavanones, flavonols, coumestans, lignans and chalcones.

Isoflavones and lignans are currently considered to make the most significant contribution to the diet. Lignans are more predominant in a typical UK diet.

Flavonoid Type Common Plant Source
Isoflavones Legumes, particularly the soy bean, clover
Lignans Most cereal, fruits and vegetables
Flavones Most red/yellow coloured fruits and vegetables
Flavanones Citrus fruit
Flavonols Most red/yellow coloured fruits and vegetables
Coumestans Bean shoots, alfalfa sprouts, sunflower seeds and oils, spinach, red beans, split peas, soy beans and some species of clover
Chalcones Liquorice and apple seeds

Not all isoflavones are oestrogenic. In clover, concentrations of isoflavones can be as high as 5% of the leaves.1 Coumestans are estimated to be 30-50 times more potent as oestrogens than the isoflavones.1 The oestrogenic activity of coumestrol is believed to be only 10-20 times lower than that of a naturally occurring oestrogen in the body, 17 beta-oestradiol.[1]

Substantial research data exist in support of the benefits of phytoestrogens to human health. Vegetarians and Japanese women eating traditional diets have a high dietary intake of phytoestrogens. Epidemiological studies suggest that the traditional Asian diet, rich in soy, is associated with a significantly lower risk of heart disease, osteoporosis, breast, prostate and colon cancer.[2]

Question marks have long existed regarding the potential downside of phytoestrogens and more recently soya products have received a bad press. How do we begin to interpret the findings and make sensible applications to our eating patterns?

It is hardly surprising that a frequent public response is to stop listening, as every time they implement something positive in their diet they find out somewhere down the line that they are likely to be doing themselves harm.

As a practitioner I prefer to stand back at such times and re-examine our origins. Heart disease, breast cancer and osteoporosis are generally considered degenerative diseases strongly associated with 20th-century Western diets and lifestyles. What would our ancestors have eaten? Which foods do the 0.01% of people that still follow a nomadic way of life consume?

The Palaeolithic Diet

Before the agricultural revolution about 10,000 years ago, the population of the world was 100% hunter-gatherer. Today only 0.01% of people follow this nomadic way of life. This involves around 400,000 people. This is the same number that existed in the 16th century when they represented 1% of the world population. Leon Chaitow, a leading naturopath and lecturer at the University of Westminster, states in his book The Stone-Age Diet that the intake of calories from meat in the Palaeolithic diet was five times that of modern Americans.3 However, the nature and quality of the meat was vastly different. There was much less saturated fat, though overall cholesterol would have been similar.

Fat intake was predominately polyunsaturated. Food remains in ancient sites include the bones of deer, bison, bear, early horse, mammoth and boar. Birds of many varieties were hunted and trapped. The estimated calorie intake was around 3,000. The intake of fibre was much higher than the modern diet and approximately one-sixth of the current salt intake was consumed.

The intake of vitamin C was very high, being nearly five times greater than the current intake. Iron and folic acid intake were plentiful.[3]

Modern-Day Nomads

The modern-day hunter-gatherer eats more fibre-rich plant foods than animal food. They like meat and seafood when available.

Eskimos rely on dried salmon, fish eggs, caribou meat and the organs of large sea animals for protein. Berries, nuts and kelp are regular components of the diet.3 They use 24 different kinds of mosses and lichens, including cloudberry, barberry, crowberry and reindeer moss. Bushmen like to eat meat when it can be caught, birds and locusts. Insects supplement the diet and ants are especially prized. Studies of bushmen in the Kalahari desert show that 19 days of hunting and gathering provided food supplies sufficient to last 100 days. The diet includes nuts, bulbs, fruits and berries.3 Water is scarce so they depend on the juices of fruits and bulbs. The Hazdas eat meat with very little value given to muscle meat. They include a wide selection of fruits, seeds and roots.[3]

The Advent of Agriculture

The widespread introduction of cereal grains into man's diet is a relatively recent event, representing a dramatic departure from those foods to which we are genetically adapted. Human beings have been on Earth for over 3 million years, but our species, Homo sapiens, is only 100,000 years old. For 90,000 years we conducted a nomadic way of life, getting our food from nature by hunting, fishing and collecting fruits, seeds, herbs and vegetables.

The discovery, in the Neolithic age, of ways to produce and store food has been the greatest revolution mankind ever experienced. The Industrial Revolution at the turn of the 17th century marked a second major change in the human diet. The milling of cereals significantly changed the quality of dietary carbohydrate.[4] The 20th century witnessed a huge increase in the intake of carbohydrates in the form of cakes, biscuits, buns, confectionery, bread, pasta and sweetened drinks. The milling of grains removes large percentages of essential nutrients, many of which are not replaced.[5] These changes have coincided with a sharp decline in physical activity, obesity, the introduction of thousands of man-made chemicals and the widespread industrial use of toxic elements.

The Challenge for the Future

Interpreting this complex biochemical 'cocktail' is now very challenging. It is clear that our diets and lifestyles bear little resemblance to our ancestors'. There is no good evidence to suggest that our physiological needs have significantly changed. The challenge for the 21st century clinical nutritionist is to help people find routes to optimizing their health in a world of scientific uncertainty and mass 'addiction' to current diets and stressful lifestyles.

Why Do Plants Make Phytoestrogens?

Researchers have to-date found around 300 plants that contain oestrogenic substances. The list includes many foods that we eat, as well as herbs and seasonings. They can be found in parsley, sage and garlic, rye, oats, wheat, barley, rice and in apples, oranges, cherries, plums and alfalfa sprouts. They can even be found in coffee and bourbon whiskey. The presence of so many oestrogenic substances in plants suggests it is not a quirk of nature.

According to Claude Hughes, a specialist in reproductive endocrinology at the Bowman Gray School of Medicine in North Carolina, who explored the effects of hormone-like compounds on the reproductive system, says that "plants are making oral contraceptives to defend themselves".[6] From an evolutionary perspective it makes sense. Plants cannot escape predators by running away. He suggests that plants lace their leaves with hormonally active substances that suppress the fertility of the animals that feed on them. Hughes says that we should keep in mind the long, shared evolutionary history between animals, including humans and the plants that we eat. He suggests that over many generations the most sensitive individuals dropped out of the population and those that were successful at reproducing passed on a certain degree of resistance.[6]

The biological activity of phytoestrogens was first identified in Australia in the 1940s when it was noted that a significant infertility problem had developed in female sheep grazing on subterranean clover.7 These animals were found to have cystic ovaries, endometriosis and infertility. Analysis of the clover revealed several phytoestrogen compounds. Their ability to exert biological activity in a range of species has since been demonstrated. So, if phytoestrogens can harm reproductive activity in animals, the possibility exists that they could do the same in humans.

Dietary Intake of Phytoestrogens

It would seem from our historic diets that we have always consumed a lot of phytoestrogens. They are present in virtually every plant. A modest intake of fruit, vegetables and cereals, typical of a current Western diet, delivers approximately 150-200mg of flavonoids a day.7 Isoflavone intake is estimated to be in the order of 30-100mg a day in populations with a high intake of soya.7 The one estimate of UK intake of isoflavones has been reported to be 1mg per day.[7] There are currently no data on intakes of lignans in the UK. Asian women are reported to eat 30-50 times as much soya as women in the West.[1]

The Gut Connection

For phytoestrogens to be of any biological use they must first be acted on by bacteria that reside in the gut.[7] The bioavailability of phytoestrogens is therefore influenced by an intact healthy gut with microflora capable of converting them into active forms. So to some extent the term 'phytoestrogen' is a misnomer. The compound found in the plant only becomes oestrogenic after passage through the human gut.[7] The active forms of phytoestrogens resulting from isoflavones are formononetin, daidzein, biochanin and genistein.[7]

Complex metabolic conversions occur in the gastrointestinal tract, resulting in the formation of an oestradiol-like metabolite, which can then be handled by the body. Once phytoestrogen metabolites have been absorbed they are then handled by the liver and undergo recycling between the gut and the liver.[7]

About 30% of human faeces are composed of bacteria.8 In fact, the number of microbial cells existing at any time in our body greatly exceeds the number of our own cells.[8] The healthy adult gastro-intestinal tract provides a suitable environment for a very large and varied population of microorganisms.[8] There are a number of factors that can affect the stability of the normal gastro-intestinal flora.

Stress, inappropriate diets and antibiotic therapy can profoundly alter the healthy balance of gut organisms.8 Antibiotics have been shown to inhibit the conversion of phytoestrogens in the gut, which might be a significant factor in a number of menopausal women's ability to utilize phytoestrogens.[7] A high-fat diet can negatively affect gut microflora.[8] Conversely a high-fibre diet helps the metabolism of phytoestrogens. Eating soya in its fermented form also appears to increase the availability of isoflavones.

Action of Phytoestrogens

Phytoestrogens are thought to confer benefit to human health both at a hormonal and a non-hormonal level.

Hormonal Effects of Phytoestrogens

Phytoestrogens are thought to be able to antagonize the action of natural oestrogen produced in the body, synthetic oestrogen or environmental oestrogens otherwise known as xenoestrogens. This is because phytoestrogens have a weak oestrogenic activity. They are purported to act as oestrogen antagonists by fitting oestrogen receptor sites on cell surfaces.

Numerous studies have shown that all the main isoflavonoids bind to oestrogen receptors and exert weak oestrogenic activity.

Premenopausally, women have an increased risk of breast cancer, fibrocystic breast disease and fibroids, all of which are associated with unopposed oestrogen made in the body, synthetic oestrogens or an excess of xenoestrogens.

Phytoestrogens are also thought to be capable of acting as oestrogen agonists. This means that phytoestrogens can fill available oestrogen receptor sites. For example, natural oestrogen production declines with the onset of menopause and it is possible that phytoestrogen can help to offset the decline by occupying available receptor sites.

The bone conserving action of soya is considered to result from the direct oestrogen receptor-mediated action of genistein on bone building cells called osteoblasts and their precursor cells.[2] Relatively recent research has identified a novel member of the nuclear receptor family named ER beta, which is found in bone tissue.[9] Phytoestrogens have been found to have a higher affinity for ER beta than oestrogen made by the body.[9] Xenoestrogens, derived from industrial and agricultural chemicals, also have a higher affinity for ER beta. It is best to avoid xenoestrogens where possible, as they are generally considered harmful. Including good levels of phytoestrogens in the diet could enable their potential protective effects to be exerted on bone tissue.

17-beta oestradiol, an oestrogen produced by the body, is known to be highly stimulating to breast and uterine tissue. Oestrone, another oestrogen produced by the body, is converted to 17-beta oestradiol. Studies in the test tube have found that both genistein and coumestral inhibit the conversion of oestrone to 17-beta oestradiol and that coumestral had the most potent effect.

45mg of soya isoflavones has been shown to lengthen the first half of the menstrual cycle, that is before ovulation, in premenopausal women.[2] Japanese women have longer cycles, and this tendency is associated with a lower risk for breast cancer though the reasons are unclear.[9] Japanese women also have lower levels of oestrogen circulating in their plasma.[9] It is perhaps the combined effect of lower oestrogen exposure and a lengthened cycle that confers protective benefits against breast cancer in premenopausal women.[9]

Serum hormone binding globulin (SHBG) is a protein that transports oestrogen around in the blood. Some researchers have found, and some have not, that lignans and isoflavones can increase the production of SHBG.[10] Higher concentrations of SHBG decrease the amount of 'free' hormone. Oestrogens in the 'free' state are biologically active. When bound to SHBG they are inactive. A stimulation of SHBG production could therefore lower the risk of hormone-dependent cancer. This supports epidemiological data that show lower SHBG values in breast cancer patients compared with healthy vegetarian women.[2]

Soy isoflavones may reduce the risk of heart disease in postmenopausal women.[2] The incidence of heart disease in postmenopausal women increases sharply and resembles the same risk for men by the time they reach 60 years. Serum cholesterol levels and the way the body handles fats alter in the postmenopausal years. Studies feeding monkeys soy isolates high in isoflavones showed significant benefits in fat profiles.[9] These findings were not apparent in those fed soy isolates in which the isoflavones had been removed, suggesting the mechanism is related to their oestrogenic activity.[9]

Some Non-Hormonal Effects of Phytoestrogens

There are several non-hormonal mechanisms in which phytoestrogens are thought to exert beneficial effects in the body.

For example, cancer cells develop their own blood supply, a process called angiogenesis, which effectively feeds the cancer and encourages a tumour to grow.[2] It is proposed that isoflavones inhibit angiogenesis, thus depriving tumours of the blood vessels that enable their growth. The proposed mechanisms of action are complex.[2]

Free radical pathology is a major theory behind the development of cancer and heart disease. Genistein and daidzein have been shown to inhibit the damaging effects of free radical activity, which can lead to tissue damage and alterations to DNA,[1] our genetic code.2 Genistein has also been shown to enhance the action of important antioxidant enzyme systems in the body, including glutathione peroxidase and superoxide dismutase.[2]

Plaque formation is central to the disease process underlying cardiovascular disease. This involves the accumulation of fats and the infiltration of immune cells into the arterial wall. The process is potentially governed by growth factors.[2] Isoflavones, particularly genistein, have been shown to alter the activity of growth factors and inhibit cell adhesion and proliferation.[2]

The Downside of Phytoestrogens

It has been established that there are considerable variations in the ways in which individuals metabolize phytoestrogens. Men and women handle phytoestrogens differently. One of the biggest problems with phytoestrogen research is interpreting the data. According to What Doctors Don't Tell You, one review of 21 studies in the test tube and in humans that involved 26 different cancer sites did show that soya isoflavones might confer protection for several cancer types.[11] However, the majority of the evidence in humans comes from studying populations, where it is virtually impossible to account for all the variables that influence health and disease.[11]Phytoestrogens are said to prevent osteoporosis. Yet, again, the evidence is based on studying populations and animal-based research.[1] Human studies have revealed small improvements in bone health and have been limited to the lower back region. Studies looking at the role of phytoestrogens for menopausal symptoms have also been mixed. In one recent study of survivors of breast cancer, 150mg of soya oestrogens per day gave less relief from hot flushes than a placebo.[11]

Because we have lived with phytoestrogens throughout our entire evolution we have to presume that we have adapted to their presence in food and can cope with eating them. A current trend is to eat more soya to obtain the beneficial oestrogenic effects.

Menopausal women, after a lifetime of low exposure to phytoestrogens, might suddenly flood their systems with soya. Some researchers are concerned about this change in dietary habit. They propose that there might be differences in Asian and Western people's responses to soya, which have evolved over generations.[1] Dr Richard Sharpe, Edinburgh based expert on male fertility from the Medical Research Council, suggests that those people traditionally eating an oriental diet may be relatively resistant to the adverse effects of phytoestrogens, whereas we may not be in the West.[1]

Sharpe is particularly concerned about the increasing use of soya in baby foods.[1] He says, "We are now exposing infants to soya in a way which hasn't happened in the past. I am seriously concerned that if soya-derived phytoestrogens are going to have an adverse effect then the time when this is most likely to occur is the first year of life."[1] Scientific evidence from animal studies is accumulating, showing how hormones can exert permanent programming effects.[1] Research from New Zealand suggests that the biological effects of phytoestrogens typically taken in by a baby drinking soya milk could be as much as a hundred times greater than the amount a child would naturally receive through breast milk.[1] In addition, breast-feeding promotes a healthy balance of gut organisms. Soya milk would not confer the same benefit. So, the question has to be asked how an infant gut would handle a regular intake of soya? Babies are no more programmed to thrive on soya than they are on cows' milk.

Human breast milk is the food of choice for babies, though it has to be said that the quality of breast milk poses concerns these days in terms of nutrient content and residues of oestrogen-like environmental chemicals. In fact, Sharpe and others support the likelihood that environmental oestrogen-like chemicals called xenoestrogens are far more potent than phytoestrogens.[1] Strong links have been made between such chemicals and the decline in male sperm count, the increased incidence of cancer of the testes and baby boys being born with reproductive abnormalities.[12] Sharpe surveyed the literature in 1993 and, even with all the uncertainties over the risks and benefits associated with soya in both adults and infants, phytoestrogens seemed an unlikely single cause of adverse reproductive changes.[1]

The Trouble with Soya

The push for more soy has been relentless and global in its reach.[13] Sales in Britain of a new soy-enriched loaf from Allied Bakeries target menopausal women seeking relief from hot flushes.[13] A quarter of a million loaves are sold each week. Mexico's humble tortilla is being turned into a soya fortified 'super tortilla' that theoretically would give a nutritional boost to nearly 20,000 Mexicans living in extreme poverty.[13]

Soya is now widely publicized as a health promoting food. Processing now makes it taste good. All age groups are turning to soya, particularly in America. Soya milk has seen the biggest gains, soaring from $2 million in 1980 to £300 million in the US in 1991.[13] Recent technological advances have turned the beany tasting beverage into one that tastes like milk shake.

A few decades ago the soybean was considered unfit to eat, even in Asia. Soya was considered a sacred grain during the Chou Dynasty (1134-246 BC), alongside wheat, barley, millet and rice.[13] However, evidence suggests that it was not a food source but was used in crop rotation.[13] Some time during the Chou Dynasty the fermentation process was discovered. This was when soya first became used as a source of food in the form of tempeh, natto, miso and soy sauce. Around the 2nd Century BC, Chinese scientists discovered how to make bean curd, now known as tofu.[13] Fermented soy products soon spread to Japan and Indonesia.

Most foods have both beneficial and negative properties. Fermenting soy seems to reduce negative compounds like growth depressants and enzyme inhibitors that can lead to gastric dysfunction. Only a long period of fermentation will reduce phytates in soya. The soybean has one of the highest levels of phytates of any grain or legume studied. Phytates can inhibit the absorption of calcium, magnesium, iron and zinc.[13] When tofu is consumed with meat, the mineral blocking effects of phytates are reduced.[13] Traditionally, the Japanese eat small amounts of tofu alongside a mineral-rich fish broth followed by meat or fish.[13] This is very different to the Western use of soya. Goitrogens, that is substances that can suppress thyroid activity, are naturally present in significant levels in soya.[13] This has been known for 50 years.

The Band-Aid Approach

We have been raised in an era where we expect a 'drug for a bug' or a 'pill for an ill'. It is clear in my mind that phytoestrogens have been plentiful in our historic diet, but not in the form of soya for the Western population. We have learnt through our 'revered' scientific method of testing one thing against one parameter that the outcome will be either negative, positive or show no effect.

Human beings are not linear organisms. The current analytical scientific method assumes a linear chain of causality that is rarely appropriate in practice. It assumes that the variance of one factor will have a negligible impact upon others in the system. This linearizing assumption is often deeply erroneous in highly complex, chaotic, self-adaptive systems such as the human body. We have difficulty enough trying to interpret scientific data based on the linear model. It will indeed be a challenge for 21st-century scientists to adopt a synergistic scientific research model! Perhaps our best model is in understanding our historic diets and lifestyles and following a way of life that supports our physiological needs.

Which Approach? – A Practitioner Perspective

As a health care professional, there is an innate tendency to want to help people feel better. Because we have been raised in a 'drug for a bug' era, it is easy to substitute a drug for a natural agent. There is a lot of evidence to support the use of phytoestrogens, so why not give a potent source in the form of soya, or a herb or, as can now be purchased, a concentrated source of isoflavones?

This is still a band-aid approach. Working with clients to balance their diets in a way that supports our physiological needs is rewarding, though definitely more challenging. Diet and lifestyle change is difficult for most of us. Swallowing a pill or potion is usually much easier and interferes with our lives minimally and we can convince ourselves we are doing our bit to make ourselves healthy.

Diversity is a key principle. Aim to eat 25 different foods a day. This will give you a wide spectrum of nutrients including phytoestrogens from a variety of sources. Instead of just eating wheat, include rye, oats, barley and rice as well. You can combine grains, which would increase variety from one grain to five or more. Have eight or preferably ten different fruits and vegetables each day. Add a variety of nuts and seeds. This will considerably bump up your variety. Add a protein source with each meal. It is not difficult to get to 25 different foods a day if you think about what you eat. Commonly we eat only six or eight different foods a day. This is because we repetitively overuse particular foods like wheat. This comes in the form of toast for breakfast, sandwiches for lunch, and pizza or pasta-based meals for dinner.

Soya is a useful example of food overuse. We hear that something is good for us, in fact it is actively promoted as good for us, and so we think the more that we eat the better. This is not necessarily the case. As described before, soya has many compounds within it that are potentially detrimental to our health. Therefore, the more we eat to gain the benefit, the more we take in of the food's negative components.

This, in my view, occurs as a direct result in the limitations of the current scientific method and media hype. There are numerous examples of how science finds out about a beneficial or harmful component of a food, the media sensationalizes the findings, and the next thing we know is that masses of people have jumped on the bandwagon.

Interestingly, in animal studies the general procedure is to nourish the animal optimally prior to experimentation. This is difficult to achieve in human studies. Instead the studies are often performed on the general 'healthy' population that are in reality in numerous stages of imbalanced health. You add, for example, concentrated levels of isoflavones to so-called healthy people and in my view it is quite possible that you will find varying responses, i.e. positive, negative and no change.

I believe there is a place for using herbs and concentrated sources of supplemented isoflavones, but not independently of dietary support. Screening can also be helpful. For example, stool tests can identify the balance of organisms living in the gut. I regularly recommend such screening prior to supplementation.

Take care before jumping on any bandwagon. Conclusive evidence is rarely available. Diversify your diet and seek professional support if you are considering supplementation and excessive dietary intakes of particular foods. The best recipe I know is to combine a wide variety of wholesome foods, that is nothing added and nothing taken away from a food, with regular exercise and de-stressing in whatever way pleases you.

Remember, stress, poor diets and antibiotics destroy the healthy balance of gut organisms which are vital for the proper use of dietary phytoestrogens in the body.

References

1. Cadbury D. The Feminization of Nature. Hamish Hamilton. 1997.
2. Mayo J. Remarkable Health Benefits of Soy Isoflavones. The Nutrition Practitioner. 1(1). February. 1999.
3. Chaitow L. The Stone-Age Diet.
4. Simopoulos AP ed. Evolutionary Aspects of Nutrition and Health, Diet, Exercise and Chronic Disease. Karger. 1999.
5. Holford P. Optimum Nutrition Bible. Piatkus. 1997.
6. Colborn T, Dumanoski D and Myers J. Our Stolen Future. Abacus. 1997.
7. Carr T. Phytoestrogens – the Biochemistry. The Nutrition Practitioner. 1(3). October. 1999.
8. Plummer N. The Lactic Acid Bacteria and Their Role in Human Health. Biomed Publications. 1992.
9. Setchell KDR and Cassidy A. Phytoestrogens – mechanisms of action and their role in human health. Module 3 MSc Programme. Antioxidants, Phytochemicals and Disease. University of Surrey. 1999.
10. Adlercreutz et al. Effect of Dietary Components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of oestrogens and sex hormone binding globulin. J Steroid Biochem. 27(4-6): 1135-1144. 1987.
11. Thomas P. Phytoestrogens – Hormone heaven or hormone havoc. What Doctors Don't Tell You. 11(5). August. 2000.
12. Neil K and Holford P. Balancing Hormones Naturally. Piatkus. 1998.
13. Fallon S and Enig M. Tragedy and Hope. The Third International Soy Symposium – Part 1. Townsend Letter for Doctors and Patients. July. 2000.

Other Sources of Information

Not-so-healthy eating: the trouble with soy, Special Report – in depth analysis of a health-food icon, Proof 2. Summer. 2000.
Martin S. Not Just Nutrition. Sorting the Soy Scare. 1(2). 2001.

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About Kate Neil

Kate Neil, RN RM DipION, is a trained nurse, midwife and nutrition consultant. Kate practises nutrition in Harley Street and Berkshire and specializes in women's health and children within the learning disorder spectrum. She is Director of NS3UK's Centre for Nutrition Education, which provides exclusive training courses in Clinical Nutrition as well as workshops for the public. She is author of Balancing Hormones Naturally and Editor of the professional journal The Nutrition Practitioner and can be reached on Tel: 01344 360 033; kate@ns3.co.uk  www.cnelm.co.uk

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