Which phytoestrogens to avoid

As anticipated, tamoxifen inhibited tumor growth but tamoxifen in conjunction with a low but not high dose isoflavone diet significantly reduced the preventative effect of this oestrogen antagonist Liu et al. In reviewing the evidence of genistein on breast cancer growth in vivo , De Lemos concluded that this phytoestrogen stimulated growth at low concentrations, but at high concentrations inhibited tumor growth.

Few in vivo studies have been carried out on other phytoestrogens although anti-tumor effects of apigenin, quercetin, and enterolactone have been reported Caltagirone et al. Animal models have also been used to look at the cancer chemoprotective effects of resveratrol. Resveratrol increased tumor latency and reduced the number of tumors in an NMU-induced mammary cancer model Bhat et al.

Several studies have investigated the effects of soy consumption on cell proliferation or biomarkers of cell proliferation in breast tissue. Hargreaves et al. These data suggest that short-term dietary soy supplementation can induce proliferation in breast tissue of premenopausal women with breast disease.

Increased mammographic density has been associated with a four- to sixfold increased risk of breast cancer Atkinson et al. Taken together, the overall evidence shows no consistent effects of dietary phytoestrogens on indicators of cell proliferation in normal human breast tissue, although phytoestrogens may increase proliferation in existing breast cancer. Whilst this review has focused on the direct action of phytoestrogens on oestrogen synthesis and oestrogen receptors in relation to breast cancer, other actions have been ascribed to these compounds that may act independently of the ER or indirectly impinge on ER signaling.

Such an effect could be significant in the progression of breast cancer although local synthesis is considered more important than circulating concentrations of hormones. Highly reactive oxygen have been shown to play a role in the development of cancer and several studies have shown that phytoestrogens can act as anti-oxidants, although the concentrations at which anti-oxidant activity is observed are unlikely to be reached through dietary means Wei et al.

Some phytoestrogens are inhibitors of cell-signaling pathways. For example, genistein is an inhibitor of protein tyrosine kinase Akiyama et al.

Resveratrol has been reported to inhibit Src tyrosine kinase and blocks Stat 3 activation in malignant cells Kotha et al. Therefore, the cellular actions of phytoestrogens may be complex.

Indeed, recent real-time RT-PCR studies in our laboratory have shown that certain phytoestrogens and low-dose mixtures of phytoestrogens are potent inhibitors of aromatase expression Rice et al. Therefore, further experiments are required to elucidate the actions of phytoestrogens on cell-signaling pathways rather than their ability to bind to oestrogen receptors.

In the early s, a possible link between isoflavones and lignans and the prevention of breast cancer was noted and this led to numerous studies to evaluate this hypothesis.

The epidemiology of breast cancer in relation to dietary intake of phytoestrogens has been adequately reviewed Adlercreutz , Ziegler and the current opinion, mainly based on studies of immigrant populations, suggests that early exposure to relatively high concentrations of soy phytoestrogens may have a protective effect on breast cancer in later life Adlercreutz Animal studies support this proposal Lamartiniere as does a recent study in Japanese women Shu et al.

However, results from epidemiologic studies are mixed, even from studies in Asian populations Yamamoto et al. Evidence relating to a high dietary intake of lignans, particularly in vegetarian diets, and the incidence of breast cancer is more controversial Adlercreutz Some studies have shown a modest reduction in breast cancer in women with a high intake of lignans McCann et al.

In contrast, it was reported that both low below the It should be noted that the metabolism of plant lignans to mammalian lignans in the gut is dependent on diet. An increase in dietary fat decreased urinary excretion of lignans whilst whole grain fiber increased the production of enterolactone see Adlercreutz There is still no conclusive evidence that a high dietary intake of phytoestrogens and the reduced incidence of breast cancer are directly related or whether phytoestrogens are simply biomarkers of a healthy diet and life-style.

Despite the evidence that some phytoestrogens at low doses can promote the growth of breast cancer cell lines and increase biomarkers of cellular proliferation in human breast cells after a short-term diet rich in phytoestrogens, current evidence would suggest that a high dietary intake of phytoestrogens does not increase the risk of breast cancer.

Many botanical preparations are sold to alleviate menopausal symptoms, but the most widely used are extracts of soy or red clover that contain isoflavones or black cohosh BC; Actaea racemosa; Wuttke et al.

Therefore, most studies investigating the efficacy of phytoestrogens as alternatives to HRT have specifically focused on the incidence, frequency, and intensity of hot flushes.

Unfortunately, most studies to date have been on a small scale and of short-term duration and the majority was not randomized, double-blind or even placebo-controlled trials Low Dog , Speeroff Equating epidemiological evidence with experimental evidence is fraught with problems. This could explain why the reduced risk of certain cancers observed among migrants increases with subsequent generations. Alternatively, this may simply reflect changing life-styles and dietary habits unrelated to phytoestrogen intake.

The question of dietary intake versus experimental doses at which phytoestrogens may exert effects is an important consideration. Reported circulating concentrations of various phytoestrogens range from nanomolar to low micromolar concentrations and yet, with the exception of in vitro studies on the growth of ER-positive breast cancer cell lines, most experiments have shown that relatively high concentrations of phytoestrogens, in the micromolar range, are required to exert any pharmacological effects, i.

It is not known, however, whether or not phytoestrogens accumulate in tissues and whether they accumulate in their conjugated forms, as they mainly exist in the circulation, or in their free active forms. Short-term dietary supplementation has been shown to have proliferative effects on breast tissue in premenopausal women with breast tumors not in women without breast disease and animal studies have provided conflicting data as to whether phytoestrogens stimulate or inhibit chemically induced tumors or tumor implants.

Generally, high concentrations of phytoestrogens are required to inhibit specific steroidogenic enzymes and hence local production of oestrogens that could be important in oestrogen-dependent breast cancers. Further work is required to determine the cellular actions of phytoestrogens beyond the oestrogen receptor and the effects of combinations of different phytoestrogens during long-term exposure. Chemical classification of the most widely investigated phytoestrogens and their major dietary sources.

Steroid synthesis in intratumoral stromal and carcinoma cells and the potential sites at which flavones and isoflavones may inhibit the production of biologically active oestrogens.

Androstenedione is converted to oestrone by aromatase. Enzymes involved in the major steroidogenic pathways that can generate biologically active oestrone and oestradiol. HSD, hydroxysteroid dehydrogenase; Arom, aromatase. AP-1 other than the specific oestrogen-response element ERE. Activation and interaction of oestrogen receptors with cell-signaling pathways and inhibition by phytoestrogens.

They also activate membrane-associated ERs 2. In turn activated kinases phosphorylate and activate oestrogen receptors 4. Activated cytosolic ERs may also modulate the activity of cell-signaling pathways dotted lines. Genistein is a potent tyrosine kinase inhibitor and inhibits signal transduction of growth factors. Apigenin inhibits PI3K and further inhibits cell signaling. The authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.

Adlercreutz H Phytoestrogens and breast cancer. Journal of Steroid Biochemistry and Molecular Biology 83 — Molecular and Cellular Endocrinology 11 77 — Progress in Cancer Research and Therapeutics 35 — Journal of Biological Chemistry — Cancer Research 61 — Environmental Health Perspectives — Archives of Biochemistry and Biophysics — Breast Cancer Research 4 1 —4.

Cancer Epidemiology, Biomarkers and Prevention 8 — Endocrine-Related Cancer 11 — Molecular Pharmacology 54 — Progress in Clinical and Biological Research — Cancer Research 66 — Journal of Steroid Biochemistry and Molecular Biology 94 — EMBO Reports 1 — Lancet — Cancer Epidemiology, Biomarkers and Prevention 10 25 — Annals of the New York Academy of Sciences — Endocrinology — Journal of the North American Menopause Society 4 89 — Annals of the New York Academy of Sciences 51 — Journal of Clinical Endocrinology and Metabolism 77 — International Journal of Cancer 87 — International Journal of Oncology 28 — International Journal of Oncology 25 — Journal of Steroid Biochemistry and Molecular Biology 72 23 — Anticancer Research 25 — Journal of the American Medical Association — Nutrition and Cancer 38 — Nutrition and Cancer 41 75 — Journal of Steroid Biochemistry and Molecular Biology 69 — British Journal of Cancer 85 — A study partially supports this theory, but more research is needed to prove whether phytoestrogens are an effective acne treatment.

There have been some claims that phytoestrogens are beneficial for fighting hormonal cancers , such as breast cancer. A study found that consuming soy foods decreased the risk of death and recurrence in women with breast cancer.

Soy foods are rich in phytoestrogens. Another study in found that phytoestrogens inhibited the growth of breast cancer cells. However, a further study suggested the role of phytoestrogens in breast cancer survival is complex and depends on what stage of menopause a woman is in.

More research is needed to fully understand whether phytoestrogens could play a useful role in cancer prevention and treatment. Phytoestrogens are not appropriate for all types of cancer. Anyone considering taking phytoestrogens should discuss it with their doctor first. Phytoestrogens may support heart health. A study found that phytoestrogens helped to treat a condition that affects the arteries and improve heart health in postmenopausal women. Studies show phytoestrogens may provide similar benefits to the synthetic estrogen used in hormone replacement therapy.

However, this does not mean that they are safer than synthetic estrogen. They act in a similar way and may carry the same risks. These may include increased risk of:. It is believed to be healthful to eat a plant-based diet, and many plant foods contain phytoestrogens. More research is needed to fully understand how phytoestrogens work, as it is not clear whether consuming them in high levels carries any health risks.

Black cohosh has traditionally been used by North American Indians for rheumatism and kidney disorders. An official drug in the US Pharmacopoeia from , it has been used in the past for the treatment of gynecological problems, including painful, heavy or absent periods, infertility, and threatened miscarriage and labor pains. In Europe, black cohosh has been a widely prescribed alternative to hormones for the management of hot flashes. In the United States it is available as a dietary supplement 20mg tablet preparation called Remifemin.

Evidence from clinical reports and observational studies on its effectiveness for relieving hot flashes has been encouraging, but again, results of studies have been mixed. Another point of controversy has to do with whether or not black cohosh has hormone-like action.

Some argue that it relieves hot flashes by working on estrogen receptors, while others suggest it has an estrogen-blocking activity. It is also unclear whether it contains phytoestrogens. Better understanding of its mode of action will help clarify whether or not black cohosh has harmful effects on the uterus and breast. Clinical trials have not shown it to have relieve vaginal atrophy or dryness during menopause. As such, women with breast cancer should avoid it until there is more information.

There have been some case reports of hepatitis and liver failure developing as an adverse reaction to black cohosh in some women. While clinical trials lasting over one year have not found serious side effects, it is recommended that women discontinue the use of black cohosh and consult their health care provider if they have a liver disorder or develop symptoms of liver problems, such as jaundice, abdominal pain or dark urine.

Other side effects include headache, stomach discomfort, rash, dizziness, and slow heart rate. Red clover. Red clover is similar to soy in that it is a legume and that contains phytoestrogens. It is marketed as a dietary supplement under the brand name Promensil. There are some case reports indicating that it helps reduce hot flashes and anxiety during menopause, but several clinical trials have found no meaningful effects as compared to the placebo.

Research on other herbs, such as ginseng Panax species , dong quai Angelica sinensis, a Chinese herb , and evening primrose oil has also not shown them to be better than a placebo in reducing hot flashes. Ginseng has been associated with uterine bleeding in postmenopausal women, and dong quai may increase the risk of bleeding in those taking anticoagulant medications, such as warfarin.

Most of these trials are small, and for effects to be significant, larger and longer trials are needed. The cruciferous vegetables, such as broccoli, cauliflower, cabbage, and Brussels sprouts, are rich in phytoestrogens Broccoli and cauliflower deliver concentrated levels of secoisolariciresinol, which is a type of lignan.

Whereas cabbage and Brussels sprouts contain coumestans, powerful plant compounds purported to have oestrogenic properties. Sprouting seeds, like alfalfa and mung bean sprouts, are a great source of phytoestrogens.

Like some cruciferous vegetables, these foods are also high in coumestans. Due to the capsaicin in chillies dilating blood vessels, spicy food can trigger flushing, sweating, and other hot flush symptoms. Consider using other spices that still pack flavour without as much heat, such as turmeric, cumin, and curry powder. Like spicy food, caffeine may increase the risk of hot flushes Reduce your caffeine intake by swapping coffee for herbal tea.

Some women find that alcohol aggravates hot flushes. Taking a break or reducing your consumption may be extremely beneficial. Not only does processed food make weight gain more likely, but it can also increase your risk for heart disease , a health condition menopausal and postmenopausal women are already more vulnerable to developing.

Want to learn more about managing your health and wellbeing in menopause? Please visit the rest of our dedicated Menopause hub. Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study. L , Andrade. JE , Helferich. Udani J. Journal of the American College of Nutrition. Egelioglu CN. Holistic Nursing Practice.

Shulman L. Yearbook of Obstetrics, Gynecology and Women's Health.