Phyto-oestrogens

What are phyto-oestrogens?¹

Phyto-oestrogens (often written as phytoestrogens) are bioactive compounds with oestrogenic activity. With the growing popularity of plant-based diets, the intake of phyto-oestrogen-rich legumes (especially soy) and legume-derived foods has increased. Evidence suggests these compounds may have an effect on hormones and health, although the results of human trials are unclear.

The intake of phyto-oestrogens has increased due to the widespread use of soy products for human consumption and as cattle food. In Europe, the lowest average intake of phytoestrogens occurs in Mediterranean countries, whereas consumption in Northern countries is 0.76 mg/day. The highest soy-derived isoflavone intakes worldwide are in China and Japan, where the population consumes an average of 15–50 mg per day, compared to only about 2 mg per day in Western countries. The promising health effects of soy have driven some people in developed countries to consume it as an alternative to meat or dairy products.

Sources of phyto-oestrogens

There are more than 20 compounds that can be found in more than 300 plants, such as herbs, grains, and fruits. The three main classes of dietary phyto-oestrogens are isoflavones, lignans, and coumestans:¹

• Isoflavones (genistein, daidzein, glycitein, and equol) are primarily found in soy beans and soy products, chickpeas and other legumes.

• Lignans (enterolactone and enterodiol) are found in oilseeds (primarily flaxseed), cereal bran, legumes, and alcohol (beer and bourbon).

• Coumestans (coumestrol) can be found in alfalfa and clover.

Most food sources containing these compounds include more than one class of phyto-oestrogens.

Effects of phyto-oestrogens^{2 3}

Various beneficial health effects have been attributed to phyto-oestrogens, such as a lowered risk of menopausal symptoms like hot flushes and osteoporosis, lowered risks of cardiovascular disease, obesity, metabolic syndrome and type 2 diabetes, brain function disorders, breast cancer, prostate cancer, bowel cancer and other cancers. In contrast to these beneficial health claims, the anti-oestrogenic properties of phytoestrogens have also raised concerns since they might act as endocrine disruptors, indicating a potential to cause adverse health effects. Given the data on potential adverse health effects, the evidence on beneficial health effects do not clearly outweigh the possible health risks, which potentially include effects on fertility, sexual development and behaviour.

Much of the evidence about phyto-oestrogens in bone metabolism is based on animal studies. Soybean protein, soy isoflavones, genistein, daidzein and coumestrol have all been shown to have a protective effect on bone in animals after oophorectomy.

In humans the evidence is conflicting:

• Phyto-oestrogens have been associated with a decreased risk of osteoporosis, but results from intervention and observational studies have been inconsistent.⁴

• Soy isoflavone supplements have been shown to significantly increase bone mineral density and decrease bone resorption.⁵

• A Cochrane review concluded there was no evidence of any effect on postmenopausal vasomotor symptoms.⁶

• There is some evidence of soya protein and/or isoflavones having beneficial effect on both blood lipid profile and bone density in postmenopausal women.⁷

• A systematic review of randomised controlled trials (RCTs) was unable to give unequivocal support for the benefit of phyto-oestrogens for the prevention of osteoporosis.⁸ There is some evidence of adverse effects on laboratory animals, but studies to assess the problem in humans are not yet forthcoming.⁹ There is also suggestion that phyto-oestrogens may enhance osteogenesis at low concentration and inhibit it at higher concentrations.¹⁰

Phyto-oestrogens and breast cancer

Some studies suggest that, unlike oestrogens, phyto-oestrogens do not appear to increase the risk of breast cancer or uterine cancer. They seem more like selective oestrogen receptor modulators (SERMs) such as raloxifene and tamoxifen.

However, in other studies, high isoflavone levels have been linked to an increased risk of breast cancer. Clearly, additional research is needed and is currently being undertaken. The effect of consumption of soy as a risk for breast cancer is controversial:

• A review concluded that the evidence was not strong in any direction and that even women who have had breast cancer may safely consume soy.¹¹

• Studies have indicated that countries with the highest phyto-oestrogen consumption have the lowest rates of breast cancer, but other epidemiological studies suggest the lack of a causative relationship.¹² Some foodstuffs are beneficial.¹³ No studies have found an increased risk of breast cancer with increased soy consumption. It may be dangerous to read too much into epidemiological studies on diet for a multifactorial condition.

• Isoflavones exhibit some antioxidant activity, which may contribute to cancer prevention.

Prostatic disease

Phyto-oestrogens are also recommended as anti-androgens and hence are of possible protective benefit with regard to carcinoma of prostate and benign prostatic hyperplasia.¹⁴ Whether they also reduce sperm count has not been examined.

Isoflavones in infants

Children with lactose intolerance or atopic eczema are often given a soya-based feed instead of milk:

• These children may have plasma phyto-oestrogen concentrations of up to 7,000 nm/L, which compares with an average of 744 nm/L in adult Japanese women.¹⁵

• The daily exposure to phyto-oestrogens from baby formula is much higher than a hormonally active dose in adults and plasma concentrations of isoflavones are much higher than endogenous oestrogen concentrations in infants. However, the only readily identified problem in these children is allergy in a small minority and also possibly inadequate intake of calcium.

• Studies following children through adolescence have not reported any obvious adverse reproductive effects.¹⁵ Nevertheless, the Chief Medical Officer (CMO) advises that soya-based infant formulas should not be used as the first choice for the management of infants with proven cow's milk sensitivity, lactose intolerance, galactokinase deficiency and galactosaemia.¹⁶ As an alternative to soya-based products, more appropriate hydrolysed protein formulas are available and can be prescribed. Soya-based formulas should only be used in exceptional circumstances to ensure adequate nutrition. For example, they may be given to infants of vegan parents who are not breast-feeding or infants who find alternatives unacceptable.

Whether or not early exposure to high doses of isoflavones has any positive or negative effects on cancer rates or cognitive and neurological parameters in later life is not yet known.

Effects on the brain

The American National Institute for Health funded a cohort study which followed 3,734 Japanese men in Hawaii who had been tracked since 1965 for a cardiovascular longitudinal study:¹⁷

• Cognitive function was assessed according to standard parameters in the living participants and their wives (aged 71-93 years).

• MRI and later autopsies looked for changes in brain tissue.

• Those who had consumed the greatest quantity of tofu in midlife had lower cognitive test performance and lower brain weight than those who had consumed the least tofu.

• The authors noted that the degree of impairment in the highest consumption versus the lowest consumption group was "roughly of the magnitude as would be caused by a four-year difference in age or a three-year difference in education."

They postulated that the observed effect might be due to isoflavones inhibiting key enzymes in oestrogen synthesis pathways. Oestrogen is known to be involved in repair of neural structures that degenerate over time, and it has been observed that higher levels of oestrogen are associated with lower incidence of Alzheimer's disease in women. Around the menopause some women become forgetful. Another study found a beneficial effect of phyto-oestrogens on mood and cognitive function in postmenopausal women.¹⁸

Thyroid function

Isoflavones in soy and flavonoids from other sources inhibit the enzyme thyroid peroxidase, which is involved in the synthesis of thyroxine. It would appear only to be a problem where there is borderline iodine deficiency.

Black cohosh

This is a substance that is recommended by herbalists for a variety of conditions and it is highly recommended for menopausal symptoms, although some authorities say that it has anti-oestrogenic effects. There are many side-effects associated with it and the European Medicines Agency has given warning about the possibility of hepatitis resulting from its use.¹⁹

Chronic kidney disease

There is weak evidence of a protective effect against the progression of chronic kidney disease by phyto-oestrogens.²⁰

Conclusion

There is a great deal of evidence about phyto-oestrogens, but there is also much confusion:

• Much of the evidence relates to animals and in vitro studies and there are questions as to how readily it should be extrapolated to humans.

• Oestrogens and similar substances are highly complex and variable. Some may have an agonistic effect on bone, an antagonistic effect on breast tissue and a neutral effect on the endometrium as we have seen with selective oestrogen receptor modulators (SERMs). There may be considerable variation with regard to the effect of plant chemicals too.

• When a substance is not given as a drug in a predetermined dose but is part of the diet, the amount ingested may be highly variable and there may also be problems such as an agonist effect at low dose and an antagonist effect at higher doses.

• Some of the results, such as those related to cognition, are contradictory. This may be due to agonists and antagonists working in different directions.

• Epidemiological studies about multifactorial diseases must be interpreted with care. When comparing different populations we cannot be sure that only one parameter is changed.

• There is very little good, long-term evidence about the effects of phyto-oestrogens in human populations. Many questions remain to be answered. If a diet high in phyto-oestrogens does protect women against breast cancer, osteoporosis and heart disease, does it also impair fertility? If it protects men against prostatic cancer, does it also impair spermatogenesis?

• The evidence to suggest that phyto-oestrogens are protective against osteoporosis is at best poor. Long-term safety is not established.