Phytoestrogens

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Phytoestrogens, sometimes called "dietary estrogens", are a diverse group of naturally occurring non steroidal plant compounds that, because of their structural similarity with estradiol (17β-estradiol), have the ability to cause estrogenic or/and antiestrogenic effects.[1]

Most common phytoestrogens found in plants
Most common phytoestrogens found in plants

Their name comes from phyto = plant and estrogen = estrus (period of fertility for female mammals) + gen = to generate.

The similarities, at molecular level, of estrogens and phytoestrogens allow them to mildly mimic and sometimes act as antagonists to estrogen[1]. Phytoestrogens were first observed in 1926 [1][2] but it was unknown if they could have any effect in human or animal metabolism. In the 1940s it was noticed for the first time that red clover (a phytoestrogens-rich plant) pastures had effects on the fertility of grazing sheep.[1][3] Researchers are still exploring the nutritional role of these substances in such diverse metabolic functions as the regulation of cholesterol, and the maintaining of proper bone density post-menopause. Evidence is accruing that phytoestrogens may have protective action against diverse health disorders such as prostate, breast, bowel, and other cancers, cardiovascular disease, brain function disorders, menopausal symptoms and osteoporosis[1][4][3]

The key structural elements crucial for the estradiol-like effects are[1]:

  • The phenolic ring that is indispensable for binding to estrogen receptors (ERs)
  • The ring of isoflavones mimicking a ring of estrogens at the receptors binding site
  • Low molecular weight similar to estrogens (MW=272)
  • Distance between two hydroxyl groups at the isoflavones nucleus similar to the occurring in estradiol
  • Optimal hydroxylation pattern

In addition to interaction with ERs, phytoestrogens may also modulate the concentration of endogenous estrogens by binding or inactivating some enzymes and may effect the bioavailability of sex hormones by binding or stimulating the synthesis of sex hormone binding globuline (SHBG).[3]

Phytoestrogens mainly belong to a large group of substituted phenolic compounds known as flavonoids: the coumestans, prenylated flavonoids and isoflavones are three of the most active in estrogenic effects in this class. The best-researched are isoflavones, which are commonly found in soy and red clover. Lignans have also been identified as phytoestrogens, although are not flavonoids[1]. Mycoestrogens (mycotoxins) have similar structures and effects, but are not components of plants, these are mold metabolites of Fusarium, a fungus that is frequently found in pastures as well as in alfalfa and clover. Although mycoestrogens are rarely taken into account in discussions about phytoestrogens, these are the compounds that initially generated the interest on the topic.[5]

Phytoestrogens cannot be considered as nutrients given that the lack of these in diet doesn't produce any characteristic deficiency syndrome nor do they participate in any essential biological function.[1]

A COT draft report from the UK Food Standards Agency presents an update of methods for a more accurate analysis of phytoestrogen content in plants and food, concluding that research in recent years is more reliable than previous studies.[6]

Contents

[edit] Ecology

These compounds in plants are an important part of their defense system mainly against fungi [7].

Phytoestrogens are considered archiestrogens (ancient, naturally occurring) and as dietary phytochemicals they are considered as co-evolutive with mammals. In human diet, phytoestrogens are not the only source of exogenous estrogens nor are they considered the largest source. Xenoestrogens (novel, man-made), which are found as food preservants and ingredients, and also in cosmetics, plastics, insecticides as well as environmentally, have a consistent influence that is added to dietary phytoestrogens, making it difficult to clearly separate the action of these two kind of agents in studies done on populations.[8]

[edit] Avian studies

The consumption of plants with unusual content of phytoestrogens under extraordinary conditions, have shown to decrease fertility in quail [9]. Parrot food as available in nature has shown only weak estrogenic activity. Studies on screening methods for environmental estrogens present in manufactured supplementary food, with the purpose to enable reproduction of endangered species. have been researched [10].

[edit] Food sources

According to a study by Canadian researchers about the content of nine common phytoestrogens in a Western diet, foods with the highest relative phytoestrogen content were nuts and oilseeds, followed by soy products, cereals and breads, legumes, meat products, and other processed foods that may contain soy, vegetables, fruits, alcoholic, and nonalcoholic beverages. Flax seed and other oilseeds contained the highest total phytoestrogen content, followed by soy bean and tofu.[11] The highest concentrations of Isoflavones are found in soy bean and soy bean products (eg. tofu) followed by legumes, whereas lignans are the primary source of phytoestrogen found in nuts and oilseeds (e.g. flax) and also found in cereals, legumes, fruits and vegetables.

Phytoestrogen content varies in different foods, and may vary significantly within the same group of foods (e.g. soy beverages, tofu) depending on processing mechanisms and type of soy bean used.[12] Legumes (in particular soybeans), whole grain cereals, and some seeds are high in phytoestrogen. A more comprehensive list of foods known to contain phytoestrogens includes: soy beans, tofu, tempeh, soy beverages, linseed (flax), sesame seeds, wheat, berries, oats, barley, dried beans, lentils, rice, alfalfa, mung beans, apples, carrots, wheat germ, ricebran, soy linseed bread, ginseng, bourbon and beer[13] fennel and anise [14]

[edit] Health Risks and Benefits

In human beings, phytoestrogens are readily absorbed, circulate in plasma and are excreted in the urine. Metabolic influence is different from that of grazing animals due to the differences between ruminant versus monogastric digestive systems.[8]

[edit] Phytoestrogen in men

The use of phytoestrogens (as soy protein) in fast food meals and other processed foods as a low-cost substitute for meat products may lead to consumption of isoflavonoids by fast food eaters. A research team at the Queen's University in Belfast, in a review article, claims that such intake may lead to a slight decrease in male fertility, including a decrease in reproductive capability if isoflavones are taken in excess during childhood. [15]

In theory, exposure to high levels of phytoestrogens in men could alter their hypothalamic-pituitary-gonadal axis. However, studies have shown that such a hormonal effect is minor. [16] Isoflavones supplementation has no effect in sperm concentration, count or motility and show no changes in testicular or ejaculate volume.[17][18] Researchers are studying if these mild effects may explain the protective effects of phytoestrogens in prostate cancer prevention. [19]

[edit] Phytoestrogen in women

There are conflicting studies, and it is unclear if phytoestrogens have any effect on the cause or prevention of cancer in women.[20][21]. While some epidemiological studies showed a protective effect against breast cancer,[22] in vitro studies concluded that women with current or past breast cancer should be aware of the risks of potential tumor growth when taking soy products, although the potential for tumor growth was found related only with small concentration of genistein and protective effects were found with larger concentrations of the same phytoestrogen.[23] A 2006 review article stated the opinion that not enough information is available, and that even if isoflavones have mechanisms to inhibit tumor growth, in vitro results justify the need to evaluate, at cellular level, the impact of isoflavones on breast tissue in women at high risk for breast cancer.[24] The generally accepted position on this topic is that phytoestrogens may be beneficial for healthy women and that women with known breast cancer should be aware of potential risks and consider avoiding consumption until more information is available.[17]

[edit] Phytoestrogen in infant formula

Some studies have found that some concentrations of isoflavones may have effects on intestinal cells. At low doses, genistein acted as a weak estrogen and stimulated cell growth; at high doses, it inhibited proliferation and altered cell cycle dynamics. This biphasic response correlates with how genistein is thought to exert its effects.[25]

Some reviews express the opinion that more research is needed to answer the question of what effect phytoestrogens may have on infants [26][27], but their authors did not find any adverse effects. Multiple studies conclude there are no adverse effects in human growth, development, or reproduction as a result of the consumption of soy-based infant formula (SBIF).[28][29][30] One of these studies, published at the Journal of Nutrition[30], concludes that:

"...there is no clinical concerns with respect to nutritional adequacy, sexual development, neurobehavioral development, immune development, or thyroid disease. SBIFs provide complete nutrition that adequately supports normal infant growth and development. FDA has accepted SBIFs as safe for use as the sole source of nutrition"

More recent clinical guidelines from the American Academy of Pediatrics state: "there is no conclusive evidence from animal, adult human, or infant populations that dietary soy isoflavones may adversely affect human development, reproduction, or endocrine function.[31]

[edit] Ethnopharmacology

for main article see Ethnopharmacology

In some countries, phytoestrogenic plants have been used for centuries in the treatment of menstrual and menopausal problems as well as for fertility problems.[32] The plants most used have been those that have later shown higher content of phytoestrogens i.e. Pueraria mirifica [33], and its close relative, kudzu[34], Angelica,[35] fennel and anise.[14]

[edit] See also

[edit] External links

[edit] References

  1. ^ a b c d e f g h Yildiz, Fatih (2005). Phytoestrogens in Functional Foods. Taylor & Francis Ltd, pp 3-5, 210-211. ISBN 978-1574445084. 
  2. ^ Varner, J E, Bonner, J (1966). Plant Biochemistry. Academic Press. ISBN 978-0121148560. 
  3. ^ a b c JOHNSTON, I (2003). Phytochem Functional Foods. CRC Press Inc, pp 66-68. ISBN 978-0849317545. 
  4. ^ Adlercreutz , Phyto-oestrogens and cancer (review article) PMID 12107024
  5. ^ Naz, Rajesh K. (1999). Endocrine Disruptors: Effects on Male and Female Reproductive Systems. CRC Press Inc, p 90. ISBN 978-0849331640. 
  6. ^ Foods Standards Agency UK
  7. ^ Richard C. Leegood, Per Lea (1998). Plant Biochemistry and Molecular Biology. John Wiley & Sons, p 211. ISBN 978-0471976837. 
  8. ^ a b Korach, Kenneth S. (1998). Reproductive and Developmental Toxicology. Marcel Dekker Ltd, pp 278-279. ISBN 978-0824798574. 
  9. ^ Phytoestrogens: adverse effect on reproduction in California quail. PMID 1246602,
  10. ^ Screening the foods of an endangered parrot, the kakapo, for oestrogenic activity using a recombinant yeast bioassay. PMID 11302429
  11. ^ Phytoestrogen content of foods consumed in Canada PMID 16898863 [1]
  12. ^ Fermented soy products have lower phytoestrogen content. Phytoestrogens and Menopause [2]
  13. ^ Assessment of the estrogenic activity of phytoestrogens isolated from bourbon and beer PMID 8116832
  14. ^ a b Fennel and anise as estrogenic agents, J. Ethnopharmacology PMID 6999244
  15. ^ Mcclure, Neil and Lewis, Sheena, West, Mhairi; Anderson, Lorraine; (September 2005), “Dietary oestrogens and male fertility potential”, Human Fertility (Taylor and Francis Ltd) 8 (3): 197--207, ISSN {1464-7273, DOI 10.1080/14647270500030266 .PMID 16234205
  16. ^ Soy protein isolates of varying isoflavone content exert minor effects on serum reproductive hormones in healthy young men. PMID 15735098
  17. ^ a b Dabrowski, Waldemar M. (2004). Toxins in Food. CRC Press Inc, p 95. ISBN 978-0849319044. 
  18. ^ Effect of a phytoestrogen food supplement on reproductive health in normal males PMID 11352776
  19. ^ Phyto-oestrogens and risk of prostate cancer in Scottish men PMID 17403269
  20. ^ Cite error: Invalid <ref> tag; no text was provided for refs named Cornell
  21. ^ Cancer Care Ontario [3]
  22. ^ Case-control study of phyto-oestrogens and breast cancer PMID 9329514
  23. ^ Ann Pharmacother. 2001 Sep;35(9):1118-21.Effects of soy phytoestrogens genistein and daidzein on breast cancer growth. de Lemos ML. Provincial Systemic Therapy Program, British Columbia Cancer Agency, Vancouver, Canada.] PMID 11573864
  24. ^ Addressing the soy and breast cancer relationship: review, commentary, and workshop proceedings. PMID 16985246
  25. ^ Genistein at a Concentration Present in Soy Infant Formula Inhibits Caco-2BBe Cell Proliferation by Causing G2/M Cell Cycle Arrest -- Chen and Donovan 134 (6): 1303 -- Journal of Nutrition
  26. ^ Soy-based formulas and phytoestrogens: a safety profile (review article) PMID 14599051
  27. ^ Isoflavones in soy infant formula: a review of evidence for endocrine and other activity in infants PMID 15189112
  28. ^ Soy protein formulas in children: no hormonal effects from long-term feeding PMID 15055353
  29. ^ Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. PMID 11497534
  30. ^ a b Safety of Soy-Based Infant Formulas Containing Isoflavones: The Clinical Evidence PMID 15113975
  31. ^ Bhatia, Jatinder (2008). "Use of Soy Protein-based Formulas in Infant Feeding PMID 18450914". Pediatrics 121 (5): 1062-1068. 
  32. ^ Muller-Schwarze, Dietland (2006). Chemical Ecology of Vertebrates. Cambridge University Press, 287. ISBN 978-0521363778. 
  33. ^ Requirement of metabolic activation for estrogenic activity of 'Pueraria mirifica" PMID 12819377
  34. ^ Analysis of isoflavones in foods and dietary supplements PMID 16915857
  35. ^ D.E. Brown, N.J. Walton, (1999). Chemicals from Plants: Perspectives on Plant Secondary Products. World Scientific Publishing, pp 21, 141. ISBN 978-9810227739.