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Phytoestrogens: Benefits, Risks, and Health Impacts

Introduction

Phytoestrogens are natural compounds present in plants and plant foods such as legumes, vegetables, and some cereals. Phyto in Greek means plant, and estrogen is a hormone found in females which regulates body functions in both women and men. Phytoestrogen imitates the body's estrogens; therefore, they are a natural hormone replacement therapy. Evidence has it that Phytoestrogens offers protection against a variety of human conditions such as breast cancer, prostate cancer, osteoporosis, cardiovascular disease, and menopausal symptoms. Although phytoestrogens have more benefits than synthetic estrogen, that does not necessarily mean that they are safer because they pose risks such as increased endometriosis, endometrial cancer, increased uterine fibroids, risk of nonviral toxic hepatitis, and changes in the hormonal cycle. There are two main categories of phytoestrogens: isoflavones found in soy, legumes such as mung beans and chicken peas, and lignans found in linseed, vegetables, and some grains (Jean, 2020). Soy sauce has no isoflavones; rather, it contains the lignin precursor called coniferyl alcohol. According to Herman et al. (1995), methodologies have been put in place to examine the number of phytoestrogens in wheat flour, meals, and other food products, which led to discovering the presence of secoisolariciresinol in soy meal. Plant oestrogens that occur naturally are categorized into five groups these are isoflavones (genistein and daidzein), lignans (SECO and MAT) that are from flaxseed, coumestans; these are found in sprouted legumes, soy sprouts and clover sprouts, resorcylic acids, lactones from green split peas and prenylated naringenin from beer and hops.

Isoflavones

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Phytoestrogens are non-steroidal plant compounds divided into flavonoids which include isoflavones, and non-flavonoids which include lignans. Isoflavones are plant flavonoids that are amongst the most estrogenic compounds. They are found in legumes which contain daidzein and genistein that exert antiestrogenic and estrogenic effects. Scientists first discovered these effects in sheep (White, 2020). The effects caused clover disease, which caused infertility related to high levels of phytoestrogens ingested from red clover, and it also caused uterine prolapse and infertility. Isoflavone phytoestrogens contain Genistein daidzein (7,40 -dihydroxyisoflavone), glycitein, biochanin, and formononetin

The figure below shows the structure of isoflavones and their glycosides (Křížová et al., 2019).

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Metabolism of isoflavone in humans

Isoflavones have different effects: antagonist or anti-oestrogenic behavior, which binds to receptors blocking oestrogen from affecting, and genistein, which inhibits breast cancer cells at>10 μM ( Křížová et al . , 2019). Agonist or oestrogenic activity binds receptors and acts as a weak oestrogen and stimulates breast cancer cells at High consumption of isoflavones led to increased length of the menstrual cycle. Soya beans are a rich source of isoflavones ( Křížová et al . , 2019). For a better examination of isoflavones, fifteen non-vegetarian premenopausal healthy women were put under test for nine months. Their dietary and activity levels were kept constant while measuring their hormonal status in the 2-3 menstrual cycle. On the first menstrual cycle, a normal diet with no soya bean was provided to them Křížová et al . , 2019. On the second cycle, six were fed on a diet that included vegetable protein with 45mg of conjugated isoflavones; three were fed with 50g of a fermented paste of soybeans containing 25mg unconjugated isoflavones, which were included in their diet over their menstrual cycle. Five of them who completed the third cycle were allowed to either eat the controlled diet over a cycle or a diet including 60gof, a soybean product containing Arcon F chemically extracted isoflavones. Soybean beans and soya bean products contain daidzein(glycoside) and genistein. (aglycone) phytoestrogen supplements from red clover are used as therapy for treating symptoms associated with menopause ( Křížová et al . , 2019). Red clover provides the methoxylated isoflavone, which is changed into daidzein in the human bodys intestinal tract.

The table below shows isoflavone composition in a variety of food (Ososki & kennedy, 2003).

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Absorption of aglycone occurs in the small intestines' proximal part by passive diffusion; after infusion to the duodenum, they reach maximal blood concentration (Křížová et al ., 2019). Plasma isoflavone concentration is reached after ingestion. Isoflavones are conjugated sugars in most soya bean protein and soybean products. Higher molecular mass and higher hydrophilicity make it hard for glycosides to be absorbed. They, therefore, are bioavailable and are metabolized when hydrolyzed. Isoflavones are hydrolyzed by the brush border membrane, and bacterial glycosidases mainly active in the early stages of life. Daidzein and genistein are absorbed and are later metabolized to glucuronides by glucuronyl transferase in the intestinal mucosa cells (Meagher & Beecher, 2000). Conjugation may take place in the liver or either location of the isoflavone ring..Metabolism of daidzein to dihydrodaidzein is converted into equol, also known as O-desmethylangolensin(O-DMA) (Křížová et al., 2019). There are two forms in which equol occurs; S- and R- equol but S- equol is the only one synthesized by the human intestinal microflora. Genistein is metabolized and converted to dihydrogenistein (Křížová et al., 2019).

Křížová et al. (2019) studied the metabolic rate of isoflavone in disimmilar cell typesand concluded that the endothelial cells use genistein and daidzein and metabolize them to sulfates, and glucuronides. Equol is not metabolized rather, it is efficiently absorbed across large intestinal walls. This fact can be proven by comparing plasma concentration of these isoflavones, whereby during the first four hours, the plasma concentration equal is. When it reaches the 24th hour, the plasma concentration of equol is at its maximum (Křížová et al., 2019). The intake of saccharide greatly influences the conversion of daidzein to equol; this is proved by using the Vivo and Vitro method (Ruiz-Larrea et al., 1997)). Bacterial fermentation is stimulated by the increase of non-starch polysaccharide intake, which results in a rise in equol production.

The pro and cons of isoflavones

sIoflavones are chemoprotective, they are also considered endocrine disruptors with possible side effects in a certain part of the population (Xiao, 2008). The organic composition of isoflavones is different from endogenous estrogens; they both have a common phenol group that enables their attachment and activation of estrogens receptors, as shown in the figure below (Křížová et al., 2019).

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The affinity of isoflavone to β-ER isoforms, situated in bones, lungs, prostate, urinary, bladder skin, and the brain, higher than the affinity α-ER isoform, which is situated on the mammary gland, testes, uterus and kidneys. Concerns have been raised over hormonal therapy's effects on treating menopausal symptoms caused by the phytoestrogen diet. Although there is a report that genistein reduces menopausal symptoms, the results are yet to be established. Taking stronger isoflavone results in a higher frequency of hot flashes. For women in their reproductive age, Isoflavones causes menstrual cycle disorder, endometriosis, and secondary infertility, and to eliminate this problem, soybean products should be left out from the diet (Xiao, 2008)

Consumption of high amounts of soybean products in a population results to lower heart disease incidences. Several risk factors are related to cardiovascular diseases, but the main risk factor is lipid abnormalities (White, 2020)). Cardiovascular diseases happen when Low-density lipoprotein (LDL) penetrates the walls of the blood vessels; free radicals then oxidize them; this leads to accumulation of LDL, which plugs blood vessels, thereby causing thrombosis. According to Křížová et al. (2019), Consuming soy protein leads to lower LDL cholesterol, and consuming soy reduces LDL cholesterol than soy proteins with no isoflavones.

Lower bone mass and constriction of bone tissues lead to osteoporosis. The condition primarily occurs in women and is related to hormone deficiency and aging. Isoflavone effects on the bone rely on the equol producer and the prophylactic effect of the (Munro et al., 2003) S- equol enhancement on the bone mass production in premenopausal women.

Recent Japanese studies have found out that high intake of soy products in young women is associated with low risks of having breast cancer in their adulthood. Studies also found out that the chances of breast cancer in Asian countries where consumption of isoflavone reaches 25-50mg, is low than in the United Kingdom where daily consumption of isoflavone is lower than 2 mg (Xiao, 2008). In Asia, soy is taken as the primary food, resulting in lower rate diseases like heart attack, breast and prostate cancer than in the United Kingdom. For instance, in Asian countries like China, the fermented form of soy is expected; it includes tempeh, miso, and tamari.

Intake of isoflavone when a child is maturing contributes to the differentiation of breast tissues leading inhibition of the anatomical structure that causes the cancer cell formation (Cassidy et al., 1995). In the USA and UK, the mortality rate of prostate cancer is higher than in Asian countries like china and japan because studies have shown the role of isoflavone in soybean ii inhibiting the progression of prostate cancer.

Hazard, Risk, and Safety

Genistin and daidzin found in soy products are considered healthy and not harmful to health; however, safety measures should be taken in women who are vulnerable or those with a history of breast cancer (patisaul and Jefferson, 2010). Isoflavones should not be taken with tamoxifen. Federal Institute for Risk Assessment in Germany advises against long-term use of isoflavone supplements.

Lignans

lignans are low molecular weight polyphenols found in plants, seeds, whole grains, and vegetables. Lignan is a Latin word meaning wood. Lignans, are formed by combining two coniferyl alcohol residues that are found in the plant cell wall. They are antifeedants used to defend the seeds and plants against animals that might consume them. Lignans is a secondary metabolite class produced by plants seeds. (Meagher & Beecher, 2000). Lignans have been discovered in roots, wooden parts, leaves, flowers, fruits, and seeds, generally low levels are partaken in the United Kingdom diet, and raises no safety concerns. Flax seeds are a source of lignans (100 mg/100 g) (Meagher & Beecher, 2000)). Sesame seed also Mammalian lignans have some oestrogenic effects and other biological properties. (Thompson LU et al.,.2013). Lignans are excreted in the urine, and originally, it was thought that the ovaries produced it. SECO, which is a result of conjugated glycoside (SDG), is the main and important lignin found in flaxseeds. Flaxseed is found in many types of food, and it contains omega-3 fatty acids, soluble and insoluble fibers, and 75-800 more lignans than other plants containing estrogen antioxidant qualities.

Benefits of lignans

Lignans found in flaxseed contain antioxidant activity, which leads to anti-cancer activities. Studies have shown that lignans are an important regimen for treating cancer (Meagher, 2000). In women, excessive intake of lignin is linked with lower risks of breast cancer. There is no connection between lignin consumption and prostate cancer and osteoporosis. Due to high intakes of flaxseeds in the Asian countries, there is a reduced risk of cancer than in the USA and UK (Touré & Xueming, 2010). Omega -3s found in flaxseeds are important in the cardiovascular system by normalizing heartbeat and anti-inflammatory action (magee, 2009). Flaxseed also helps in hardening the arteries to prevent deposition of plaque in the arteries and preventing white blood cells from gluing in the blood vessels' inner linings (milder, 2005). Eating flaxseeds helps in controlling cholesterol levels in the bloodstream linked with heart diseases. Lignans have Biological activities that include Oestrogenic/anti-oestrogenic effects. Enterolactone stimulates (oestrogenic effect) MCF-7 breast cancer cell propagation in the same way as oestradiol (1 nM (Touré & Xueming, 2010).

Hazard, Risk, and Safety

Pregnant women and breastfeeding mothers because it may result in negative effects in the offspring’s (magee, 2009). Experts have it that it is safer to consume flaxseed than flax oil to get all nutrients. Flax seeds have a potential of preventing colon, skin and skin cancer.it is however recommended to use 50g of flaxseeds per day

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Conclusion

Phytoestrogens have many physiological effects on a person. Their bioavailability is the uppermost of all compounds. Being useful and valuable or having antagonistic effects have been reported so far for these compounds of phytoestrogens. Basing on the hypothesis that they had always been incorporated in the human diet, they are considered inactive. isoflavone exposure is modern due to changes in soy's cooking process this results to the compounds being considered for what they are, i.e., estrogenic compounds, exerting endocrine-disrupting effects with other anthropoid compounds recently liberated in the environment. Studies shows that their most adverse impact is experienced in women during reproduction. Their risky and life threatening effects are already established estrogen-dependent cancers seem to occur at higher doses based on toxicology studies. These effects are counterbalanced by a preventive impact, probably due interaction at the initial breast cancer progression step. More mechanistic data are required to ascertain this mechanism. More research is still necessary to take the best part of these compounds, the question of their endocrine-disrupting effect should be taken into consideration. In the risk assessment, modern soy formula carries no risk to infants. There is little evidence of disruption to fertility – beneficial for prostate cancer.

References

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Murkies, A. L., Wilcox, G., & Davis, S. R. (1998). Phytoestrogens. The Journal of Clinical Endocrinology & Metabolism, 83(2), 297-303.

Touré, A., & Xueming, X. (2010). Flaxseed lignans: source, biosynthesis, metabolism, antioxidant activity, bio‐active components, and health benefits. Comprehensive reviews in food science and food safety, 9(3), 261-269.

Magee Elaine, (2009, September 3). The benefits of flaxseed. WebMD. https://www.webmd.com/diet/features/benefits-of-flaxseed

White, A. (2020, September 2). Phytoestrogens: Benefits, menopause, side effects, and food. Healthline. https://www.healthline.com/health/phytoestrogens

Jean Hailes. (2020, January 15). Phytoestrogens. https://www.jeanhailes.org.au/health-a-z/healthy-living/nutrients/phytoestrogens

Patisaul H and Jefferson W. (2010, March 27). The pros and cons of phytoestrogens. PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074428

Křížová, L., Dadáková, K., Kašparovská, J., & Kašparovský, T. (2019). Isoflavones. Molecules, 24(6), 1076.

Munro, I. C., Harwood, M., Hlywka, J. J., Stephen, A. M., Doull, J., Flamm, W. G., & Adlercreutz, H. (2003). Soy isoflavones: a safety review. Nutrition reviews, 61(1), 1-33.

Xiao, C. W. (2008). Health effects of soy protein and isoflavones in humans. The Journal of nutrition, 138(6), 1244S-1249S.

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