What foods are high in estrogen

Plant derived estrogens or phytoestrogens are found in a wide variety of foods, most notably soy ¹. Phytoestrogens are present in many human foodstuffs including fruits (plum, pear, apple grape berries, …), vegetables (beans, sprouts, cabbage, spinach, soybeans, grains, hops, garlic, onion,…), wine, tea, and they have been identified in a number of botanical dietary supplements. Phytoestrogens are strikingly similar in chemical structure to the mammalian estrogen, estradiol, and bind to estrogen receptors (ERs) with the preference for ERβ ². This suggests that these compounds may exert tissue specific effects, beside other non receptor mediated biological activities, as antioxidant capacity and antiproliferative/antiangiogenic effects.

Estrogen Replacement Therapy has many demonstrated benefits, including decreases in bone loss, fractures and tooth loss; decreased risk of myocardial infarction, gastrointestinal cancer and colon cancer; delay of onset of Alzheimer’s disease; and probable decrease in age-related macular degeneration and reversal of urogenital atrophy. Unfortunately, Estrogen Replacement Therapy is also associated with elevated risk of gallstones, deep vein thrombosis and endometrial cancer, and there is growing evidence that Estrogen Replacement Therapy may also be associated with a moderate increase in risk of breast cancer. Even a modest increase in cancer risk may be problematic, since long term Estrogen Replacement Therapy may be required to achieve desired effects such as cardioprotection and prevention of osteoporosis.

Plants vary intra- and inter-species in the types and concentrations of phytoestrogens due to variables in plant growth, soil, weather conditions and the age of plant. Chemically phytoestrogens are phenolic phytochemicals or polyphenols. These are the largest category of phytochemicals and the most widely distributed in the plant kingdom ³. They include a wide variety of structurally different compounds such as isoflavones, mainly found in soy, lignans found in grains, stilbenes found in the skin of grapes. Other less investigated compounds include flavones, flavans, isoflavanes and coumestans. Phytoestrogens are also present in numerous dietary supplements and widely marketed as a natural alternative to estrogen replacement therapy.

Table 1. Main chemical categories of phytoestrogens

Lignans	Flavonols	Coumestans	Isoflavones	Stilbenes
Enterolactone	Quercetin	Cumestrol	Glycitein	Resveratrol
Enterodiol	Rutin		Genistein
			Daidzein

Note: The phytoestrogens classification is controversial, currently phytoestrogens can be subdivided in four main classes: flavonoids (flavones and isoflavones), lignans, coumenstans and stilbenes

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Although in test tube and animal studies provide preliminary plausible mechanisms to explain how phytoestrogens act, the applications of diets rich in such compounds and their consequent biological effects still need to be fully examined, tested and confirmed through traditional scientific experimental pathway.

The question of whether or not phytoestrogens are beneficial or harmful to human health remains unresolved. Unfortunately, due to the great diversity of phytoestrogen compounds, including different bioavailability, pharmacokinetics, pharmacological properties and metabolic fates, it is quite complex to define, assess and understand their precise effects on human health since large and time extended intervention studies are needed. Plus the answer is likely to be complex and may depend on age, health status, and even the presence or absence of specific gut microflora. Clarity on this issue is needed because global consumption is rapidly increasing.

Natural estrogens are involved in a multiplicity of programmed events in target tissues as uterus, breast, pituitary gland and hormone responsive tumors. The initiation of estrogen action by all of the estrogens is considered to be the same in each target tissue. Estrogen firstly bind to the nuclear ER (estrogen receptor), then an estrogenic ligand causes a conformational change that encourages dimerization and interaction with either specific DNA sequences or a protein-protein interaction with AP-1 or Sp1 sites in the promoter region of estrogen-responsive genes ⁵. These events herald the biological effects of estrogen in the specific target tissue or tumor. A small percentage (2-3%) of estrogen receptors are located on the cell membrane and contribute to non genomic effects of estrogen ⁶. Two estrogen receptors are currently known, ERα and ERβ. Although the two estrogen receptors can be localized within the same cell, they vary in tissue distributions and can have different effects on mixed agonist and antagonist molecules.

Table 2. Dietary sources of phytoestrogens (foods with estrogen)

Group	Subgroup	Examples	Dietary sources
17β-Estradiol	Endogenous Estrogen	N/A	N/A
Polyphenols		Resveratrol	Grape skin, red wine
Flavonoids	Flavanones	Eriodictyol, Hesperetin, Homoeriodictyol,Naringenin	Citrus fruits and juices
	Flavones	Apigenin, Luteolin, Tangeritin	Parsley, celery, capsicum pepper
	Flavonols	Fisetin, Kaempferol, Myricetin, Pachypodol, Quercetin, Rhamnazin	Kale, broccoli, onions tomatoes, lettuce, apples, grapes, red wine
	Catechins	Proanthocyanides	Chocolate, green tea, beans, apricots, cherries, berries
Isoflavonoids	Isoflavones	Biochanin A, Clycitein, Daidzein, Formononetin, Genistein	Soy beans, and other legumes
	Isoflavans	Equol	Metabolite of daidzein
	Coumestans	Coumestrol	Clover, alfalfa, spinach

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Phytoestrogens are structurally and/or functionally similar to mammalian estrogens and their active metabolites (Table 1). One major class is the lignans, which are components of plant cell walls and found in many fiber-rich foods such as berries, seeds (particularly flaxseeds), grains, nuts and fruits. Most phytoestrogens, however, are phenolic compounds of which the isoflavones and coumestans are the most widely researched groups. Isoflavones are present in berries, wine, grains and nuts, but are most abundant in soybeans and other legumes ⁸. The isoflavone content of an array of foods is now published in numerous on-line databases [reviewed in Schwartz et al. ⁹] the most accessible of which for consumers is maintained by the USDA (Table 2) United States Department of Agriculture [281].

Table 3. Isoflavone content of a representative sample of food products

Food product	Genistein (mg/100g)	Daidzein (mg/100g)	Total isoflavones (mg/100 g)
Soy Infant Formula (powder)	13.5	6.32	26.3
Edamame (raw green soybeans)	22.6	20.3	48.9
Miso	23.2	16.4	41.5
Silken tofu	8.4	9.2	18.0
Raw tofu, regular	13	9	23
Textured soy flour	89.4	67.7	172.6
Soy protein isolate	57	31	91
Soy-based sliced cheese	6.5	5.1	14.5
Soy-based bacon bits	45.8	64.4	118.5
Soy-based burgers	5.0	2.4	6.4
Red clover	10	11	21
Multigrain bread	0.2	0.2	0.4
KASHI Go Lean cereal	7.7	8.4	17.4
Green tea, Japanese	0.02	0.01	0.02
Flaxseeds	0.04	0.02	0.07
Raw broccoli	0.00	0.04	0.25

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Table 4. Isoflavones and lignans in various food sources

Plant species (Common name)	Genistein	Daidzein	Secoisolariciresinol	Metairesinol
Soybean	993-3115	413-2205	< 1-8	< 1
Kidney bean	< 1-19	< 1-2	2-4	< 1
American groundnut	4-30	< 1	< 1-2	< 1
Chicpea	3-8	< 1-8	< 1	0
Pea	< 1	< 1	< 1	< 1
Lentil	< 1	< 1	< 1	< 1
Kudzu root	467	7283	< 1	< 1
Flaxseed	0	0	10-247	30
Sunflower seed	< 1	6	2	17
Peanut	2	1	8	< 1
Wheat bran	< 1	< 1	3	0
Barley	< 1	< 1	2	0
Rye bran	0	4	4	5
Strawberry	0	0	33	< 1
Cranberry	0	0	29	0
Bluberry	0	0	23	0
Rasberry	0	0	4	0
Red cabbage	< 1	< 1	4	< 1
Broccoli	< 1	< 1	11	< 1
Garlic	0	0	11	< 1
Zucchini	0	0	23	< 1
Carrot	0	0	10	< 1
Breetroot	0	0	3	< 1
Black tea	Trace	Trace	73	12
Green tea	Trace	Trace	75	5

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Types of Food Estrogens

Flavonoids

They are the largest group of plant phenols including more than 4000 different compounds which are the most studied phytochemicals. The basic flavonoid structure allows a multitude of variations in chemical structure, giving rise to flavonols (quercetin, kaempferol, myricetin), flavones (apigenin, luteolin), flavanones (catechin, epicatechin), antocyanidins and isoflavonoids (glycitein, genistein, daidzein) ¹¹. An important effect of flavonoids is the scavenging of oxygen-derived free radicals. The major source of isoflavonoids in the diet is from soy-based foods. The isoflavonoids from legumes, including genistein and daidzein, are the most studied phytoestrogens. They can exist as glycosides or as aglycones, the glucosides being readily hydrolized in the gut as their aglycones. The aglycones are easily transported across intestinal epithelial cells. Genistein has one-third the potency of estradiol when interacts with ERα, and one thousandth of the potency of estradiol when it interacts with ERβ as determined by expression of luciferase reporter gene construct in kidney cells that have been cotransfected with ERα and ERβ ¹². Genistein may produce similar effects to estradiol in several different tissues as breast, ovarian, endometria, prostate, vascular , bone tissue and cell lines ¹³. Furthermore, genistein induce also responses that are not associated with the ER, as the inhibition of tyrosine kinase and DNA topoisomerase ¹⁴. Such effect is produced even in the presence of the antiestrogen revealing a non genomic action that could explain a part of the difference between genistein and estradiol.

In vitro experimental systems also showed that flavonoids possess anti-inflammatory, antiallergic, antiviral and anticarcinogenic properties ¹⁵ and various of these molecules, notably isoflavonoids, are identified as phytoestrogens being able to bind estrogens receptors, and possess estrogenic or antiestrogenic activities ¹⁶.

Lignans

They are constituens of higher plants, such as whole grains, legumes, vegetables and seeds with exceptionally high concentrations of lignans found in flaxseed. Although previously though to be present only in higher plants, mammalian lignans have been detected in the biological fluids of humans and animals. The chemical structure of plant lignans is very different from that of mammalian lignans and most of the changes occur in the colon, liver and small intestine. Enterolactone and enterodiol are metabolites of the plant lignans metairesinol e secoisolariciresinol, respectively ¹⁷. A clinical study showed that the excretion of the lignans, enterodiol and enterolactone, was significantly higher during a carotenoid (carrots and spinaches) and cruciferous (broccoli and cauliflowers) vegetable diet, than during a vegetable-free diet ¹⁸.

Coumestans

Legumes are the main source of coumestrol, the coumestan showing the highest estrogenic activity, and low level of coumestrol have been found also in brussel sprouts and spinaches, while the highest concentrations are reported in clover and in soybean sprouts.

Stilbenes

Recently, also the stilben resveratrol has been identified as a phytoestrogen. Resveratrol is a natural compound produced by some plants, such as grapevines, in response to injury. Peanuts are rich in resveratrol too. Polygonium cuspidatum roots, which have long been used in traditional oriental medicine, have been identified as the major active source of stilben phytoalexins. Trans resveratrol was firstly detected in grapevines in 1976 by Langcake and Pryce, who found that this compound was synthesized by leaf tissues in response to Botrytis cinerea fungal infection or exposure to ultraviolet light ¹⁹.

The biological activity of resveratrol was attested about fifteen years ago by the health benefits obtained by orally administered resveratrol. An experimental study suggested that an average drinker of wine may, in the long term, absorb a quantity of resveratrol sufficient to explain the beneficial effect of red wine on human health ²⁰. Resveratrol possesses anticancer properties, antioxidant activity and some observations have challenged the protective effects of resveratrol against atherosclerosis then preventing cardiovascular diseases. As a phytoestrogen it may favourably influence several physiological processes and given that resveratrol has a different structure, also its mechanism of action might differ somewhat from that of other flavonoids ²⁰.

References

1. Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Frontiers in neuroendocrinology. 2010;31(4):400-419. doi:10.1016/j.yfrne.2010.03.003. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074428/
2. Cassidy A. Potential risks and benefits of phytoestrogen-rich diets. Int J Vitam Nutr Res. 2003;Mar. https://www.ncbi.nlm.nih.gov/pubmed/12747219
3. UCLA Center for Human Nutrition Phytoestrogens at http://www.cellinteractive.com/ucla/natural_remedies/phytoestrogens.html 26/04/2004
4. Bacciottini L, Falchetti A, Pampaloni B, Bartolini E, Carossino AM, Brandi ML. Phytoestrogens: food or drug? Clinical Cases in Mineral and Bone Metabolism. 2007;4(2):123-130. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781234/
5. Jordan VC, Mc Gregor Schafer J, Levenson AS, et al. Molecolar classification of estrogens. Cancer Res. 2001;September 15(61):6619–23. http://cancerres.aacrjournals.org/content/61/18/6619.long
6. Chen DB, Bird IM, Zheng J, et al. Membrane estrogen receptor-dependent extracellular signal-regulated kinase pathway mediates acutet activation of endothelial nitric oxide synthase by estrogen in uterine artery endothelial cells. Endocrinology. 2004;145:113–25. https://www.ncbi.nlm.nih.gov/pubmed/14512434
7. Whitten PL, Kudo S, Okubo KK. Isoflavonoids. In: D’Mello JPF, editor. Handbook of Plant and Fungal Toxicants. Boca Raton: CRC Press; 1997. pp. 117–137.
8. Dietary phytoestrogens. Kurzer MS, Xu X. Annu Rev Nutr. 1997; 17():353-81. http://www.annualreviews.org/doi/full/10.1146/annurev.nutr.17.1.353
9. Schwartz H, Sontag G, Plumb J. Inventory of phytoestrogen databases. Food Chem. 2009;113:736–747.
10. United States Department of Agriculture (Agricultural Research Service) Database for the Isoflavone Content of Selected Foods, Release 2.0. 2008.
11. UCLA Center for Human Nutrition – Flavonoids and health at http://www.cellinteractive.com/ucla/natural_remedies/flavonoids.html
12. Kuiper GG, Lemmen JG, Carlsson B, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β Endocrinology. 1998;139:4252–4263. https://www.ncbi.nlm.nih.gov/pubmed/9751507
13. Zhou S, Turgeman G, Harris Stephen E, et al. Estrogens activate bone morphogenetic protein-2 gene trascription in mouse mesenchymal stem cells. Mol Endocrinol. 2003;17:56–66. https://www.ncbi.nlm.nih.gov/pubmed/12511606
14. Jonas J, Plant T, Gilon P, et al. Multiple effects and stimulation of insulin secretion by the tyrosine kinase inhibitor genistein in normal mouse islets. Br J Pharmacol. 1995;114:872–880. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1510214/
15. Nijveldt RJ., van Nood E., van Hoorn DEC, et al. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001;74:418–25. http://ajcn.nutrition.org/content/74/4/418.long
16. Prouillet C, Mazière JC, Mazière C, et al. Stimulatory effect of naturally occurring flavonols querceetin and kaempferol on alkaline phosphatase activity in MG-63 human osteoblast through ERK and estrogen receptor pathway. Biochem Pharmacol. 2004;67:1307–13. https://www.ncbi.nlm.nih.gov/pubmed/15013846
17. Tham DM, Gardner CD, Haskell WL. Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223–35. https://www.ncbi.nlm.nih.gov/pubmed/9661587
18. Kirkman LM, Lampe JW, Campbell DR, et al. Urinary lignan and isoflavonoid excretion in man and women consuming vegetable and soy diet. Nutr Cancer. 1995;24:1–12. https://www.ncbi.nlm.nih.gov/pubmed/7491293
19. Frémont L. Biological effects of resveratrol. Life Sciences. 2000;66(8):663–73. https://www.ncbi.nlm.nih.gov/pubmed/10680575
20. Bertelli A, Bertelli AA, Gozzini A, et al. Plasma and tissue resveratrol concentrations and pharmacological activity. Drugs Exp Clin Res. 1998;24(3):133–8. https://www.ncbi.nlm.nih.gov/pubmed/9825229