Phytoestrogens are compounds in plant foods (“phyto” means plant) that are similar in shape to the hormone oestrogen. In the past, this understandably led to concerns about whether it would be safe for women who had had hormone dependent cancers to eat food sources of phytoestrogens. After all, if a woman was having treatment to either reduce oestrogen levels in the body as much as possible, or to prevent oestrogen from binding to oestrogen receptors, then couldn’t there be a risk that phytoestrogens would undermine the therapy? Let’s dive into the science to find out.
Phytoestrogen-Rich Foods
Phytoestrogens exist in a wide variety of plant foods, such as legumes, seeds, vegetables, fruit, grains and even tea (green and black). Soy and flaxseeds contain particularly high amounts of phytoestrogens, and as these are the foods that have been the best studied in relation to their impact on cancer risk and cancer recurrence, they are the focus of this blog post.
The main phytoestrogens in soy are genistein and daidzein, which belong to a class of compounds called isoflavones. The phytoestrogens in flax are called lignans. Certain gut bacteria can transform them, producing new compounds which can have even greater phytoestrogenic properties. This means that our individual exposure to phytoestrogens is not just dependent on how much of them we eat, but on how our gut metabolises them.
Oestrogen Receptors
First, let’s consider how oestrogen can stimulate cancer cell growth. Hormone receptive cancer cells carry receptors for oestrogen. Oestrogen molecules can bind onto those receptors much as a key fits into a lock. When oestrogen binds to the receptor, it turns on genes that are involved in growth and thus can keep a tumour growing. There are two types of oestrogen receptors, ERα and ERβ. ERα is clearly linked to tumour growth. The role of ERβ is less clear, but there is some evidence that in hormone receptor positive cancers, ERβ might act protectively, suppressing uncontrolled cell growth(1).
Phytoestrogens also bind to oestrogen receptors, but less strongly than a woman’s own oestrogen does. Although phytoestrogens can bind to both ERα and ERβ, when eaten in normal dietary quantities many phytoestrogens preferentially bind to ERβ(2). This suggests that eating a diet containing phytoestrogens might be protective against breast cancer and other hormone dependent cancers.
Phytoestrogens may also affect oestrogen metabolism and might even alter the amount of a woman’s own oestrogen in circulation, although evidence for these effects is conflicting.
Anticancer Effects Beyond Oestrogen
Phytoestrogens such as isoflavones and lignans have anticancer actions that are independent of oestrogen, meaning that they can be valuable to include in your diet no matter what type of cancer you have had. They are antioxidants and inhibit key cancer signalling pathways. They can regulate gene activity, including upregulating the protective BRCA1 gene. They inhibit angiogenesis (the formation of cancer’s blood supply) and metastasis, induce apoptosis (programmed cell death) and can induce a process called cell cycle arrest, which stops cancer cells from dividing(3), (4).
Phytoestrogens can inhibit breast cancer stem cells(2), (5). This is of interest because while medical cancer treatments may destroy the bulk of a tumour, some stem cells may remain, and it is hypothesised that these may contribute to treatment resistance or to the spread of cancer(6).
Effects on Cancer Outcomes
The scientific mechanisms are interesting (well, they are to me anyway!), but what counts is what happens in real life.
Let’s look at soy first. A 2017 study(7) of over 6000 women in the US who had been diagnosed with breast cancer showed that those who ate the highest amount of dietary isoflavones (greater than 1.5mg per day) had a 21% decrease in all-cause mortality compared with those who ate the lowest amount, but only in women who had had oestrogen receptor negative tumours. However, there were no negative effects from eating soy on women with oestrogen receptor positive tumours, or those on endocrine therapy.
An earlier 2012 study(8) looked at data on over 9000 breast cancer survivors in the US and in China, and found that daily consumption of more than 10mg of isoflavones was associated with a non-significant reduction in all-cause mortality (13%) and breast cancer-specific mortality (17%), and a significant 25% reduction in recurrence risk, when compared to intakes of less than 4mg per day. It is interesting to note that the amounts of isoflavones studied here were much higher than those used in the 2017 study. Among oestrogen receptor positive breast cancers, women taking Tamoxifen experienced the greatest benefit in recurrence risk reduction by eating soy.
There is less evidence on how dietary soy intake affects other cancers. A 2015 systematic review and meta-analysis(9) concluded that dietary soy intake was inversely associated with the risk of endometrial cancer, but did not investigate how eating soy after diagnosis might affect cancer outcomes.
Studies on soy isoflavone supplementation have resulted in contradictory findings, although some reported an increase in the expression of cancer-promoting genes as a response to taking soy isoflavone supplements(10), (11). We do not have evidence on how this affects cancer outcomes, but it does suggest that higher, supplemental doses of soy could be harmful after a breast cancer diagnosis. This may be due to the fact that whilst normal dietary doses of phytoestrogens bind to ERβ in preference to ERα, soy isoflavone supplements contain much higher doses, and these can bind to ERα just as strongly as they bind to ERβ(12).
Together, these studies indicate that consumption of soy in food form after a breast cancer diagnosis is safe and may even provide survival benefits for some, such as women who have had oestrogen receptor negative breast cancers. Higher dose soy isoflavone supplements should be avoided.
There is much less evidence on lignans (from flaxseeds). A 2021 systematic review and meta-analysis(13) concluded that intake of lignans is protective in postmenopausal women with breast cancer, as higher intakes were associated with a 28% reduction in the risk of breast cancer-specific mortality. However, they saw that higher lignan intakes were associated with poorer survival in premenopausal women, although there were limitations in how the researchers were able to assess this data. Nevertheless, at this point we can only say that increasing the amount of flaxseeds in the diet is safe for postmenopausal women with a hormone receptor positive cancer.
Do Phytoestrogens help with Menopausal Symptoms?
Phytoestrogens have a long history of traditional use in managing the symptoms of menopause, particularly hot flushes and night sweats. This was tested as recently as 2023(14). 84 postmenopausal women who experienced hot flushes were randomised into two groups. The first group was advised to follow a low fat, vegan diet which included 86g of cooked soybeans daily, whilst the second group was advised to follow their usual diet. In the dietary intervention group, moderate to severe hot flushes decreased by 88%, compared to 34% in the control group. After 12 weeks, 50% of women in the dietary intervention group had no moderate to severe hot flushes at all, whilst there had been no change in the control group.
The drop in oestrogen at menopause contributes to an increased risk of poorer cardiometabolic health, with postmenopausal women being at higher risk of obesity, diabetes and cardiovascular disease than premenopausal women. It has been suggested that phytoestrogens may reduce disease risk. Some animal studies support this, but there is little human data(15).
There is some human data to support the view that soy isoflavones can improve postmenopausal bone mineral density, but the studies have been using high dose supplements which are not safe for use after a hormone dependent cancer(16).
Recommended Dietary Sources
Soy is available in many forms, and it can be tricky to know what to choose! As ever, it is important to think holistically and to avoid consuming large quantities of ultra-processed foods just because they contain soy. Soy made into fake meat products is not soy as nature intended it! Unprocessed forms of soy that can be good to include in your diet are tempeh, tofu, miso and soy sauce (or tamari if you prefer a gluten-free option). 100g tofu typically provides 25-30mg of isoflavones; tempeh a little more. The 2017 study discussed above on soy consumption after breast cancer showed that amounts of soy isoflavones as small as 1.5mg per day could improve breast cancer outcomes; as you can see, this amount is very easily achievable.
Here are some ideas for including unprocessed soy in your diet:
Add cubes of firm tofu to a vegetable stir fry
Add silken tofu to a smoothie or blend it into a creamy sauce
Mix miso paste with lemon juice and olive oil to create a salad dressing with an Asian tang
Marinate tempeh before cooking and adding to a veggie bowl as your source of protein
Flaxseeds can be bought whole or ground. Whole flaxseeds are often sold as linseeds; the two plants are related and are very similar, and the terms are sometimes used interchangeably. Linseeds/flaxseeds come in brown or golden varieties, and nutritionally it does not matter which you choose. Whole flaxseed tends to travel through the gut undigested, so it is best to eat ground flaxseeds in order to absorb nutrients, including the lignans. However, flaxseeds contain delicate oils which can oxidise rapidly once the seeds are ground. For best results, buy whole flaxseeds and grind them just before you eat them, in a blender or a coffee grinder. Alternatively, if you buy ready milled flaxseeds, be sure to store them in a sealed container in the fridge after opening the packet. Note that flaxseed oil does not contain the phytoestrogenic lignans that the seeds do.
The easiest way of adding flaxseeds to your diet is to eat them along with yoghurt and fruit. You can also incorporate flaxseeds into breads, crackers and other baked goods.
This month’s recipe book has some more ideas for you, using both soy and flaxseeds.
Don’t forget that by eating a wide range of plant foods that includes legumes other than soy, nuts, seeds, whole grains, vegetables and berries, you will obtain smaller but valuable amounts of phytoestrogens. Phytoestrogens don’t exist in isolation in plants, so by aiming to eat more of them, you will also be obtaining fibre, vitamins, antioxidants and other beneficial phytonutrients.
References
(1) Zhou, Y. and Liu, X. (2020). ‘The role of estrogen receptor beta in breast cancer’, Biomarker Research, 8 (39). Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487630/
(2) Farhat, E.K., Sher, E.K., Džidić-Krivić, A. et al. (2023). ‘Functional biotransformation of phytoestrogens by gut microbiota with impact on cancer treatment’, the Journal of Nutritional Biochemistry, 118, 109368. Available at https://www.sciencedirect.com/science/article/pii/S0955286323001018?via%3Dihub
(3) Banerjee, S., Li, Y., Wang, Z. et al. (2008). ‘Multi-targeted Therapy of Cancer by Genistein’, Cancer Letters, 269(2), pp226-242. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575691/
(4) Jang, W.Y., Kim, M.-Y. and Cho, J.Y. (2022). ‘Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites’, International Journal of Molecular Sciences, 23, 15482. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778916/
(5) Nguyen, M. and Osipo, C. (2022). ‘Targeting Breast Cancer Stem Cells Using Naturally Occurring Phytoestrogens’, International Journal of Molecular Sciences, 23, 6813. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224163/
(6) Khan, S., Suryavanshi, M., Kaur, J. et al. (2021). ‘Stem cell therapy: A paradigm shift in breast cancer treatment’, World Journal of Stem Cells, 13(7), pp841-860. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316873/
(7) Zhang, F.F., Haslam, D.E., Terry, M.B. et al. (2017). ‘Dietary Isoflavone Intake and All-Cause Mortality in Breast Cancer Survivors: the Breast Cancer Family Registry’, Cancer, 123(11), pp2070-2079. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444962/
(8) Nechuta, S.J., Caan, B.J., Chen, W.Y. et al. (2012). ‘Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women’, The American Journal of Clinical Nutrition, 96(1), pp123-132. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374736/
(9) Zhang, G.-Q., Chen, J.-L., Liu, Q. et al. (2015). ‘Soy Intake Is Associated With Lower Endometrial Cancer Risk’, Medicine (Baltimore), 94(50), e2281. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058928/
(10)Khan, S.A., Chatterton, R.T., Michel, N. et al. (2012). ‘Soy Isoflavone Supplementation for Breast Cancer Risk Reduction: A Randomized Phase II Trial’, Cancer Prevention Research, 5(2), pp309-319. Available at http://cancerpreventionresearch.aacrjournals.org/content/5/2/309.long
(11)Shike, M., Doane, A.S., Russo, L. et al. (2014). ‘The Effects of Soy Supplementation on Gene Expression in Breast Cancer: A Randomized Placebo-Controlled Study’, Journal of the National Cancer Institute, 106(9). Available at http://jnci.oxfordjournals.org/content/106/9/dju189.long
(12)Jiang. Y., Gong, P., Madak-Erdogan, Z. et al. (2013). ‘Mechanisms enforcing the estrogen receptor β selectivity of botanical estrogens’, The FASEB Journal, 27(11), 4406-4418. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804744/
(13)Liu, Z., Fei, Y.-J., Cao, X.-H. et al. (2021). ‘Lignans intake and enterolactone concentration and prognosis of breast cancer: a systematic review and meta-analysis’, Journal of Cancer, 12(9), pp2787-2796. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040718/
(14)Barnard, N.D., Kahleova, H., Holtz, D.N. et al. (2023). ‘A dietary intervention for vasomotor symptoms of menopause: a randomized, controlled trial’, Menopause, 30(1), pp80-87. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812421/
(15)Leonard, L.M., Choi, M.S. and Cross, T.-W.L. (2022). ‘Maximizing the Estrogenic Potential of Soy Isoflavones through the Gut Microbiome: Implication for Cardiometabolic Health in Postmenopausal Women’, Nutrients, 14(3), 553. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8840243/
(16)Canivenc-Lavier, M.-C. and Bennetau-Pelissero, C. (2023). ‘Phytoestrogens and Health Effects’, Nutrients, 15(2), 317. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864699/
Thank you. This is really helpful.