The Strength of Soy

Image author: Madeline Chan

Written by: Alexa Di Pede

For the majority of the world’s population, taking prescription medication is a mainstay of one’s life experience. In a clinical setting, synthetic drugs are often presented as the only treatment option. To be able to mitigate disease with a carefully-selected grocery list may seem like fiction. However, evidence suggests that this may be the reality for post-menopausal women who are at risk for osteoporosis. Synthetic hormone replacement therapy (HRT) has been at the forefront of pharmaceutical interventions for post-menopausal osteoporosis for the last 60 years, and up until twenty years ago, it was the only preventative treatment on the market that provided relief from deteriorating bone mineral density. Synthetic hormone replacement therapy, though the most effective for short term prevention, has been associated with an array of adverse effects. A study conducted by the Women’s Health Initiative concluded that HRTs can potentially increase the risk for coronary heart disease (HR=1.29), breast cancer (HR=1.26), stroke (HR=1.41), and pulmonary embolism (HR=2.13). In the case of synthetic estrogen in particular, HRTs may have the ability to promote the growth of carcinogenic cells[1]. One of the most prominent shortcomings of prolonged HRT use is that they are only effective during the duration of prescription; once discontinued, a relapse of bone deterioration ensues[2].  In light of the risks incidence and severity, it becomes evident that the outcomes of prolonged HRT use does not justify HRT-related adverse reactions[3]. As a result women who may benefit from HRT are hesitant to pursue this form of treatment due to fear of contraindications[11].  

Is there an alternative?

Over the last 30 years, as information has become increasingly accessible, patients have become more informed about overall health and seek alternatives alongside their physicians to dictate courses of treatment.  In accordance with the general trend of trust in natural or non-pharmacological treatments, post-menopausal women often resort to more primitive alternatives in the prevention of disease [3]. One such intervention that has grown in popularity are phytoestrogens, which have become more appealing over the last few decades in preventing and combating post-menopausal osteoporosis. 

The precedent for such trends may be traced to the relationship between diet and bone health in Asian populations, who have been practicing herbal medicinal treatments for hundreds of years. Soy has long been the foundation of many traditional asian diets, and it is an ingredient that has been empirically proven to reduce the risk for post-menopausal osteoporosis. Phytoestrogens, a class of compounds found in a variety of soy derivatives, were first implicated in osteoporosis prevention when scientists determined that Asian women were 40% less likely to develop osteoporosis than western women[4]. Amazed, researchers were curious as to what aspect of the asian diet made these women more resistant towards the development of osteoporosis. It became evident that the high levels of soy (isoflavonoid) consumption —a trend that is  naturally apparent in many traditional Asian diets— was responsible for such observations. The finding was corroborated by the fact that Asian immigrants living in Western nations were equally susceptible to developing post-menopausal osteoporosis as other female populations;  Asian immigrants tend to have “Westernized” diets that incorporate more protein and fat relative to their Eastern-residing counterparts, while simultaneously having reduced fibre and soy intake [3]. This finding has allowed researchers to utilize food as an indicator of one’s risk of developing post-menopausal osteoporosis. Although the optimal quantity and type of soy intake required to support bone health has yet to be elucidated, dietary pattern evidence suggests that regular consumption of soy foods is likely to be useful for optimal sustentation[12]. Given that the effects of phytoestrogens are similar to that of HRTs on a variety of cellular receptors, patients and physicians tend to perceive the use of soy phytoestrogens as overwhelmingly positive, while their synthetic counterparts are receiving increasing rates of congressional and public concern[9]. This suggests that the healthcare needs should be approached with a multifaceted evaluation of risk factors and perception of the prescribed treatment. Often the first-line pharmaceuticals for a post-menopausal osteoporosis  may not be effective for all affected women, fueling the necessity for empowering individuals with knowledge about alternatives. 

Phytoestrogens: How do they work?

The onset of menopause is characterized by the cessation of ovarian function[5], which halts the production of estrogen — a vital female-dominant hormone which prevents bone density deterioration by averting microfractures and penetrative reabsorption. This leaves post menopausal women at very high risk for developing osteoporosis, which is a disorder of decreased bone mass, microarchitectural deterioration, and fragility fractures due to subsequent estrogen deficiency[6]. Many of the major diseases of Western populations are hormone-dependent and epidemiologic data has shown a strong association between their incidence and the components of diet[2]. 

Phytoestrogens represent a diverse group of non-steroidal natural products, which seem to have some consistent effects on osteoporosis prevention[5]. Isoflavinoids, the most predominant category of phytoestrogens are believed to work by binding to estrogen receptors (ERs) that are found on cell membranes, much like the body’s own estrogens do. Naturally, isoflavones are sugar-bound (glycoside) and are biologically inactive. To exert effects, they must be metabolized from their inactive constituents into their active free form (aglycone) by the gastrointestinal tract. It is vital to take into consideration that the extent to which the metabolism of glycosides occurs is highly dependent on variables such as diet, microflora, and the use of antibiotics. Much like their endogenous counterparts (estrogens), phytoestrogens are biotransformed by bacteria found in the intestinal microbiome before being absorbed into enterohepatic circulation. Once metabolized, these derivatives reach circulating concentrations that exceed the amounts of endogenous estrogens by several orders of magnitude. Isoflavinoids and genistein in particular have been shown to be more potent than any other known phytoestrogen when their in vitro oestrogenic activity was compared with that of 17β-estradiol (E2)[7]. In most systems, the relative binding affinities of genistein and isoflavonoids are greater for ER-β than for ER-α, while E2 binds to both receptors with approximately equal affinities [10]. As osteoporosis results in the imbalance between the reabsorptive activity of osteoclasts and bone-building activity of osteoblasts,, phytoestrogens may provide enhancing effects on bone mineral density, bone turnover markers, and bone mechanical strength due to the inhibition of bone resorption[13]. These phytoestrogens and their metabolites have many potent hormonal and nonhormonal activities that may explain some of their observed biological effects[3].  The protective capacity of phytoestrogens pose as a potentially preferential alternative to HRT in postmenopausal women,  as they consequently act as a preventative agent against osteoporosis without many of the adverse affects that coincide with HRT use[14].  Phytoestrogens are found in a wide variety of plant foods including soy protein, whole grains, fruits, beans, seeds, amongst others, and may offer the most potential for the prevention of bone loss by reducing the expected deterioration of trabecular bone and bone mineral density. Even though the relative strength and efficacy of phytoestrogens in the acute maintenance of bone mass is inferior to its synthetic counterparts, their avenue of treatment remains favourable when analyzing long-term outcomes of osteoporosis prevention as well as subsequent adverse effects. 

As the incidence of osteoporosis gradually increases among western populations, at-risk post-menopausal women should be encouraged to consume more phytoestrogens in order to curb the reliance on HRT as a primary treatment avenue. Like many other diseases, osteoporosis lies on a spectrum, and its relative severity between individuals may be quite varied, fueling the notion that HRTs are unlikely to be the best option for every patient’s case and circumstance. In a clinical setting, natural alternatives may be presented by the physician in order to tailor treatment for the highest degree of efficacy. Whether incorporating these derivatives into diet through whole foods, or opting for a direct over the counter option (ipriflavone), women should more frequently consider phytoestrogens as a preventative agent, even in the absence of substantial predetermined risk. As with any exogenous compound, there are benefits and harms affiliated with moderate consumption of soy[9]. With regards to the general population of post-menopausal women, alarm over soy derivatives is likely dispensable, but so is the idea that a high soy diet will mitigate all ills. The risk-benefit analysis of data studied up to date suggests that there are a number of factors that may affect an individuals risk, and thus treatments need to be customized considering both synthetic interventions and diet as options that can be implemented both separately or synergistically together.

Citations 

[1] Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-33. doi: 10.1001/jama.288.3.321.

[2]Setchell KD. Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr. 1998;68(6 Suppl):1333S-1346S. doi: 10.1093/ajcn/68.6.1333S. 

[3]Setchell KD. Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr. 1998;68(6 Suppl):1333S-1346S. doi: 10.1093/ajcn/68.6.1333S.

[4]Cauley JA. Defining ethnic and racial differences in osteoporosis and fragility fractures. Clin Orthop Relat Res. 2011;469(7):1891-9. doi: 10.1007/s11999-011-1863-5. 

[5]Poluzzi E, Piccinni C, Raschi E, Rampa A, Recanatini M, De Ponti F. Phytoestrogens in postmenopause: the state of the art from a chemical, pharmacological and regulatory perspective. Curr Med Chem. 2014;21(4):417-36. doi: 10.2174/09298673113206660297.

[6]Lane JM, Russell L, Khan SN. Osteoporosis. Clin Orthop Relat Res. 2000;(372):139-50. doi: 10.1097/00003086-200003000-00016. 

[7]Milligan SR, Kalita JC, Heyerick A, Rong H, De Cooman L, De Keukeleire D. Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. J Clin Endocrinol Metab. 1999;84(6):2249-52. doi: 10.1210/jcem.84.6.5887. 

[8]Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2012;(7):CD004143. doi: 10.1002/14651858.CD004143

[9]Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Front Neuroendocrinol. 2010;31(4):400-19. doi: 10.1016/j.yfrne.2010.03.003..

[10] Messina M, McCaskill-Stevens W, Lampe JW. Addressing the soy and breast cancer relationship: review, commentary, and workshop proceedings. J Natl Cancer Inst. 2006;98(18):1275-84. doi: 10.1093/jnci/djj356. 

[11]Arjmandi BH. The role of phytoestrogens in the prevention and treatment of osteoporosis in ovarian hormone deficiency. J Am Coll Nutr. 2001(5 Suppl):398S-402S; discussion 417S-420S. doi: 10.1080/07315724.2001.10719175. 

[12]Lanou AJ. Soy foods: are they useful for optimal bone health? Ther Adv Musculoskelet Dis. 2011(6):293-300. doi: 10.1177/1759720X11417749

[13]Fu SW, Zeng GF, Zong SH, Zhang ZY, Zou B, Fang Y, Lu L, Xiao DQ. Systematic review and meta-analysis of the bone protective effect of phytoestrogens on osteoporosis in ovariectomized rats. Nutr Res. 2014 Jun;34(6):467-77. doi: 10.1016/j.nutres.2014.05.003. 

[14]Franke AA, Halm BM, Kakazu K, Li X, Custer LJ. Phytoestrogenic isoflavonoids in epidemiologic and clinical research. Drug Test Anal. 2009 (1):14-21. doi: 10.1002/dta.12

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