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In recent years, there has been a growing interest in the potential health benefits of phytoestrogens, a diverse group of naturally occurring compounds found in plants. These compounds, with structural similarities to estrogen, are found in foods such as soybeans, flaxseeds and sesame seeds, and are studied for their roles in modulating hormonal activity and antioxidant properties. Their estrogen-like functions make them particularly interesting in managing conditions exacerbated by hormonal imbalances, such as type 2 diabetes, obesity, cardiovascular diseases, and osteoporosis. Phytoestrogens enhance insulin sensitivity and glucose metabolism, while their anti-oxidant properties neutralize free radicals and inhibit lipid peroxidation. They also influence fat metabolism and reduce adipogenesis, addressing oxidative stress and inflammation. Their estrogenic effects improve bone mineral density and reduce fracture risks, particularly in postmenopausal women, highlighting their broad potential in metabolic disease management. This growing body of research suggests that phytoestrogens, due to their unique properties and diverse mechanisms of action, could be a valuable addition to dietary and therapeutic strategies in the prevention and management of various metabolic diseases. This chapter delves into the multifaceted roles of phytoestrogens in metabolic disorders, with a special focus on their antioxidant properties.
Raghuveer Singh Government (P.G.) College, Lalitpur, Uttar Pradesh, India
Brijesh Kumar Singh*
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore
Madhulika Tripathi*
Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore
*Address all correspondence to: singhbrijeshk@duke-nus.edu.sg and madhulika.triptahi@duke-nus.edu.sg
1. Introduction
The potential health benefits of phytoestrogens have grown exponentially. These naturally occurring compounds, abundant in plants (Table 1) like soybeans (Glycine max L.) rich in isoflavones such as genistein and daidzein, and flaxseeds (Linum usitatissimum L.) abundant in lignans, like secoisolariciresinol diglucoside, share structural similarities with the hormone estrogen [1]. Moreover, red clover’s (Trifolium pratense L.) isoflavones, including formononetin and biochanin A, black cohosh’s (Actaea racemosa L.) triterpene glycosides, like cimicifugoside and actein, these phytoestrogens have garnered attention for their potential therapeutic applications [2] and have spurred extensive research into their effects on various metabolic diseases.
Plant’s common name (scientific name)
Compound’s nature (compound names)
Alfalfa (Medicago sativa L.):
Coumestans (e.g., medicagol)
Apricots (Prunus armeniaca L.):
Coumarins (e.g., bergapten)
Barley (Hordeum vulgare L.L.):
Lignans (e.g., matairesinol)
Black Cohosh (Actaea racemosa L.):
Triterpene glycosides (e.g., cimicifugoside and actein)
Buckwheat (Fagopyrum esculentum Moench):
Lignans (e.g., secoisolariciresinol)
Cabbage (Brassica oleracea var. acephala var. capitata L.):
Isoflavones (e.g., coumestrol)
Chickpeas (Cicer arietinum L.):
Isoflavones (e.g., genistein and daidzein)
Coffee (Coffea arabica L.):
Lignans (e.g., pinoresinol)
Dong Quai (Angelica sinensis (Oliv.) Diels.):
Coumarins (e.g., ligustilide)
Fennel (Foeniculum vulgare Mill.):
Coumarins (e.g., bergapten)
Flaxseeds (Linum usitatissimum L.):
Lignans (e.g., secoisolariciresinol diglucoside, and matairesinol)
Isoflavones (e.g., genistein, daidzein, and glycitein)
Sunflower Seeds (Helianthus annuus L.):
Lignans (e.g., lariciresinol)
Table 1.
Common plants rich in phytoestrogens along with their corresponding compounds.
In this chapter, we explore the complex web of interactions orchestrated by phytoestrogens at an organismal level during metabolic diseases [3, 4]. Beyond their estrogenic properties, which hold the key to their potential therapeutic applications, we place a special emphasis on their often overlooked yet equally significant role as potent antioxidants [5, 6]. These dual capabilities of phytoestrogens not only show promise in addressing metabolic disorders but also hint at a broader potential for promoting overall health and well-being. Throughout this exploration, we uncover the possible mechanisms by which phytoestrogens interact with cellular receptors, shedding light on their potential to modulate hormonal responses. Additionally, we scrutinize accumulating evidence that supports their efficacy in mitigating metabolic diseases, ranging from type 2 diabetes to obesity and cardiovascular conditions. Alongside this, we illuminate their crucial role in buffering against oxidative stress, a cornerstone of many chronic health challenges. This chapter also aims to unravel the multifaceted roles of phytoestrogens, positioning them not merely as dietary components but as potential allies in the pursuit of metabolic health and longevity. By doing so, we hope to foster a deeper understanding of the profound impact that these natural compounds can have on our well-being and inspire further research into their therapeutic applications.
These plants (Table 1) contain varying concentrations of phytoestrogens, and their effects on the body can differ depending on factors such as dosage, individual physiology, and overall diet. It is important to note that while these compounds can exert estrogenic effects, they are much milder than the natural hormone estrogen, and their impact may vary from person to person.
Phytoestrogens, a group of naturally occurring compounds derived from plants, have garnered significant interest for their potential health benefits and improvements in overall metabolism [6, 7]. These compounds share structural similarities with the hormone estrogen (Figure 1) and have been the subject of extensive research regarding their impact on various aspects of human health [8, 9].
Figure 1.
Structural similarity between naturally produced estrogen hormone (17beta-estradiol, E2) and phytoestrogens coumesterol (coumestans) genistein (isoflavones), and pinoresinol (lignan). The structures are from PubChem compounds (https://pubchem.ncbi.nlm.nih.gov).
Classified into three main categories—isoflavones, lignans, and coumestans—phytoestrogens are widely distributed in numerous plant-based foods [10]. These include soybeans, flaxseeds, legumes, and an array of fruits and vegetables. The diversity of their sources highlights the potential for incorporating phytoestrogens into a balanced diet (Table 1).
2.1 Classification, sources, and bioavailability of phytoestrogens
Phytoestrogens belong to the group of polyphenolic compounds and can be categorized into three main classes: isoflavones, lignans, and coumestans [9]. Prominent dietary sources of phytoestrogens include soybeans, flaxseeds, legumes, and various fruits and vegetables [6]. Phytoestrogens have potential health benefits due to their unique properties [7]. The most prominent phytoestrogens are as follows.
2.1.1 Isoflavones
These are perhaps the most well-known phytoestrogens and are commonly found in soy-based products such as soybeans and tofu. Isoflavones are characterized by their distinct arrangement of phenolic rings. Prominent isoflavones include genistein, daidzein, and glycitein. In addition to soy, isoflavones are present in various legumes and some fruits. Isoflavones are known for their potent estrogenic effects and numerous health benefits.
While isoflavones have health benefits, they may also have some potential side effects for certain individuals. These side effects include hormonal disruptions, gastrointestinal discomfort, rare allergic reactions, possible thyroid function interference, and reproductive effects, especially in supplement form. Isoflavones may interact with medications (levothyroxine, tamoxifen, anticoagulants, etc.), affecting hormone levels and raising concerns about breast tissue effects, although conclusive evidence is lacking. Consuming isoflavones in moderation within a balanced diet is recommended, as they offer potential health advantages, like reducing the risk of specific chronic diseases.
2.1.2 Lignans
Lignans, another class of phytoestrogens, are abundant in seeds and grains, with flaxseeds being one of the richest sources. Secoisolariciresinol diglucoside and matairesinol are notable lignans. Beyond flaxseeds, lignans are found in sesame seeds, whole grains, and certain vegetables. Lignans are prominent polyphenols recognized for their complex chemical structures, which often comprise multiple phenolic rings. Lignans exhibit remarkable antioxidant properties and have garnered attention for their potential impact on human health.
Lignans are generally considered safe and beneficial for health. However, while they exhibit mild estrogenic properties, the side effects of lignans are typically minimal and less common compared to other phytoestrogens. Some individuals may experience temporary gastrointestinal discomfort like gas or bloating when consuming large amounts of lignan-rich foods, and rare allergic reactions are possible. Lignans may also interact with medications (antiplatelet and anticoagulant, Synthroid, etc.), necessitating consultation with a healthcare provider if one is on such medications. Overall, lignans are known for their antioxidant properties and potential contributions to heart health and disease prevention.
2.1.3 Coumestans
While less studied than isoflavones and lignans, coumestans are present in various plants, including clover, alfalfa, and bean sprouts. Formononetin and coumestrol are representative coumestans. These compounds contribute to the phytoestrogen content of leguminous plants. However, less studied compared to isoflavones and lignans, coumestans like coumestrol have shown promise in research for their potential health benefits.
While there is less research on their side effects than isoflavones and lignans, excessive consumption of coumestan-rich foods may lead to mild gastrointestinal discomfort. However, this is less common than other phytoestrogens, and rare allergic reactions are possible. Coumestans may also interact with medications affecting hormone levels, especially during hormone replacement therapy, necessitating consultation with healthcare providers for those on such medications. Further, coumestans with antioxidant supplements, such as vitamin C or vitamin E, may have a combinatorial effect. Despite limited research, coumestans like coumestrol have shown promise for their antioxidant properties and potential health contributions.
2.1.4 Daily recommended dosage of phytoestrogens
It is important to note that there is no specific recommended daily allowance (RDA) for phytoestrogens and intake recommendations may vary among health organizations and countries. Additionally, individual tolerance and response to isoflavones can vary. Some people may consume higher amounts without adverse effects, while others may be more sensitive.
The recommended daily dose of isoflavones and lignans can vary depending on factors such as age, gender, health status, and individual dietary preferences. Isoflavones and lignans are typically consumed through dietary sources rather than supplements, and their intake can vary widely among different populations, such as one to two servings of soy-based foods (tofu, soy milk, edamame, or tempeh), legumes, ground flaxseeds, or sesame seeds per day can provide a reasonable amount of isoflavones. A typical serving size is around 3 to 4 ounces (85 to 113 grams). Coumestans are generally not consumed in isolation, and they are not commonly available as supplements. Clover and Alfalfa Sprouts can be added to salads and sandwiches, while beans and legumes can be consumed to fulfill daily requirements for coumestans.
2.1.5 Improving digestibility and bioavailability of phytoestrogens
Phytoestrogens, lignans in particular, are recognized for their antioxidant properties, which may help protect cells from oxidative damage caused by free radicals. While they are strong antioxidants in vitro, the extent of their antioxidant activity in the human body can vary depending on factors such as food preparation and digestion. The bioavailability of phytoestrogens can be limited because they are bound to dietary fiber and need to be released and absorbed in the digestive tract. In this regard, various strategies can be utilized to increase their bioavailability, such as grinding flaxseeds before consumption can break down the seed’s protective outer layer, making the lignans more accessible for absorption. Sprouting certain seeds, grains, or legumes can increase the bioavailability of phytoestrogens, including lignans. Consuming lignan-rich foods with sources of healthy fats, such as nuts, seeds, or avocados, may enhance the absorption of fat-soluble lignans. Fermentation can also increase the availability of phytoestrogens.
Beyond the aforementioned examples, various fruits, vegetables, nuts, and seeds also contribute to our dietary intake of phytoestrogens. This diverse range of sources highlights the prevalence of these compounds in our diets and focuses on the need for further research to understand their potential impact on human health. Next, we will explore the distinct properties and biological activities of these phytoestrogen classes, shedding light on their role in metabolic diseases and their antioxidant capabilities.
2.2 Estrogenic activity
Phytoestrogens closely resemble the structure of estrogen (Figure 1) and are currently a major focus of research in the field of metabolic health. These natural substances, which are present in a wide range of plants, interact with the body’s estrogen receptors, thereby influencing hormonal functions and physiological reactions. This characteristic forms the basis of their potential utility in managing metabolic diseases. Isoflavones, notably genistein and daidzein found in soybeans, are prime examples of phytoestrogens with significant estrogenic activity [2, 8]. Their ability to bind to estrogen receptors facilitates cellular responses similar to those triggered by natural estrogen. This interaction holds implications for various health aspects, ranging from bone density modulation to cholesterol level regulation [11].
Lignans, particularly abundant in flaxseeds, such as secoisolariciresinol and matairesinol, also exhibit estrogenic potential. Their interaction with estrogen receptors can mimic estrogen’s actions, contributing to hormonal balance and potentially offering protection against conditions like osteoporosis [12]. Red clover, another key source, contains isoflavones like formononetin and biochanin A, which exhibit estrogenic effects. Additionally, the presence of coumestrol, a coumestan found in various clover species, though less studied, indicates its potential role in hormonal health due to its affinity for estrogen receptors [13]. Hops, particularly rich in the flavonoid xanthohumol, expand the diversity of phytoestrogens in the diet [14]. These compounds interact with estrogen receptors, adding to the overall estrogenic activity observed in phytoestrogen-rich foods.
The unique interaction of phytoestrogens with estrogen receptors has sparked considerable scientific interest, especially regarding their potential therapeutic applications in metabolic diseases [3, 4, 11]. Research has been exploring how these compounds, through their estrogenic activity, may enhance insulin sensitivity, regulate glucose metabolism, and affect adipose tissue function [15]. Their role in cardiovascular health, particularly in regulating lipid profiles, blood pressure, and endothelial function, is also under investigation [16]. Moreover, the estrogen-like effects of phytoestrogens on bone health offer potential benefits in preventing osteoporosis [17].
The complex interplay between phytoestrogens and estrogen receptors demonstrates a delicate balance within the body’s endocrine system. This relationship not only underlines the potential therapeutic applications of phytoestrogens but also highlights the importance of dietary sources rich in these compounds. Foods like soybeans, flaxseeds, clover, and hops are not just nutritionally valuable but also offer potential health benefits due to their phytoestrogen content. As research progresses, our understanding of the multifaceted effects of phytoestrogens is expected to deepen. This knowledge will be crucial for developing innovative strategies to leverage phytoestrogens in promoting health and well-being, particularly for individuals dealing with metabolic disorders. The exploration of phytoestrogens thus represents a significant area of interest in nutritional science and therapeutic research, with the potential to impact public health positively.
Phytoestrogens, natural compounds found in plants, have shown promise in influencing metabolic health [8]. Notably, isoflavones, prevalent in soybeans and legumes, exhibit potential in improving insulin sensitivity, holding promise for type 2 diabetes management [15]. Additionally, phytoestrogens may play a role in regulating adipose tissue metabolism, suggesting their relevance in addressing obesity [4]. Their potential impact on cardiovascular health is also noteworthy, with evidence suggesting benefits in blood pressure regulation and cholesterol levels [18]. Moreover, lignans from sources like flaxseeds and sesame seeds show promise in supporting bone health, indicating potential adjunctive treatments for osteoporosis. This section illuminates the multifaceted contributions of phytoestrogens to various facets of metabolic well-being.
3.1 Type 2 diabetes mellitus
Type 2 diabetes mellitus (T2DM) represents a significant global health challenge characterized by insulin resistance and impaired glucose metabolism. In this context, phytoestrogens have emerged as a focal point of research, particularly regarding their potential to improve insulin sensitivity and glucose regulation. Among the diverse phytoestrogen sources, soybeans and flaxseeds have shown considerable promise in mitigating the complexities associated with T2DM [18].
Isoflavones, primarily found in soybeans (Glycine max L.), such as genistein and daidzein, have been the subject of extensive studies. These compounds have been observed to enhance insulin sensitivity and modulate glucose metabolism, acting as insulin sensitizers and potentially reducing insulin resistance. Flaxseeds (Linum usitatissimum L.), rich in lignans like secoisolariciresinol diglucoside and matairesinol, present an alternative phytoestrogen source with demonstrated efficacy in T2DM. Studies also indicate that lignan supplementation in T2DM patients led to improved glycemic control, highlighting their potential role in managing this metabolic disorder [19]. Expanding beyond soybeans and flaxseeds, red clover (Trifolium pratense L.), with its rich content of isoflavones like formononetin and biochanin A, has also shown potential in improving insulin resistance. This was evidenced in research by Liu et al. in 2013 (published in the American Journal of Clinical Nutrition), suggesting that red clover isoflavones could offer additional benefits in T2DM treatment strategies [20].
The inclusion of phytoestrogen-rich foods like soybeans, flaxseeds, and red clover in dietary regimes may provide comprehensive benefits in the management of T2DM. Furthermore, exploring other sources such as pumpkin seeds (Cucurbita pepo), known for their lignan content, and chia seeds (Salvia hispanica), rich in alpha-linolenic acid and lignans, broadens the scope for personalized dietary approaches to metabolic health. This expanding research on phytoestrogens and their influence on metabolic disorders like T2DM highlights their potential as adjunctive therapeutic agents [19]. As our understanding deepens, integrating these phytoestrogens into dietary and therapeutic strategies presents a promising frontier in the holistic management of T2DM, potentially enhancing standard treatment protocols and improving patient outcomes.
Potential Contraindications: Some diabetes medications may interact with phytoestrogens in foods like soy and supplements. Sulfonylureas, such as glipizide and glyburide, stimulate insulin release and excessive phytoestrogen intake can affect blood sugar levels, potentially leading to hypoglycemia. Thiazolidinediones like pioglitazone and rosiglitazone improve insulin sensitivity, and phytoestrogens, particularly isoflavones, may have similar effects, potentially influencing medication efficacy. Alpha-glucosidase Inhibitors, such as acarbose and miglitol, slow carbohydrate digestion, but excessive dietary fiber from sources like flaxseeds or whole grains can impact medication absorption. While DPP-4 inhibitors like sitagliptin and saxagliptin enhance insulin release, monitoring blood glucose levels is advisable if significant dietary changes involving phytoestrogens are made.
3.2 Obesity
Phytoestrogens, naturally occurring compounds found in various plants, have become a focal point in obesity research due to their potential role in modulating adipose tissue metabolism and reducing fat accumulation. Their effects on lipid profiles and adipogenesis suggest they could be valuable in combating obesity.
Soybeans (Glycine max L.), known for their rich isoflavone content, including genistein and daidzein, have shown promise in regulating adipose tissue. Research has particularly highlighted genistein’s ability to modulate adipogenesis, which is the process of developing mature fat cells from precursor cells. By inhibiting adipocyte differentiation, genistein may help regulate fat accumulation, offering a potential pathway for managing obesity [21]. Flaxseeds (Linum usitatissimum L.) are another significant source of phytoestrogens, especially lignans like secoisolariciresinol diglucoside and matairesinol. Studies indicate that these lignans may positively influence body composition by reducing fat mass, suggesting their utility in weight management strategies [22].
Red clover (Trifolium pratense L.), with its isoflavones formononetin and biochanin A, also emerges as a noteworthy player in the obesity context. Research suggests that these compounds may impact lipid metabolism, contributing to decreased fat accumulation [23]. Additionally, Pueraria (Kudzu) (Pueraria lobata (Willd.) Ohwi), rich in isoflavones like puerarin and daidzein, has attracted attention for its potential to improve lipid profiles. Studies demonstrate that puerarin might reduce total cholesterol and triglycerides, positioning it as a promising compound for obesity management [24].
The scope of phytoestrogens in tackling obesity extends further. Chia seeds (Salvia hispanica), known for their alpha-linolenic acid and lignan content, have been recognized for their potential in weight management [25]. These seeds may aid in improving metabolic markers and reducing fat accumulation. Alfalfa (Medicago sativa L.), containing coumestans such as medicagol, presents another interesting avenue in obesity research [26]. While coumestans are less studied than isoflavones and lignans, they offer a novel area of exploration in the context of metabolic health.
The growing body of evidence underscores the potential of a variety of phytoestrogen-rich plants in addressing obesity. As such, there is no specific recommended dose of phytoestrogens for managing obesity because individual responses can differ, and more research is needed to establish clear guidelines. In animal studies focused on obesity and diabetes, soy protein has demonstrated the ability to lower serum insulin levels and improve insulin sensitivity. Human studies, both with and without diabetes, have also indicated that soy protein can help regulate blood sugar levels, reduce body weight, lower elevated lipid levels, and decrease excessive insulin production. These findings suggest favorable effects of soy protein on both obesity and diabetes. However, it is important to note that most of these clinical trials were relatively short in duration and involved a limited number of participants. Furthermore, the specific components of soy protein and flaxseed responsible for these benefits remain uncertain. It is unclear whether isoflavones (such as daidzein and genistein), lignans (including matairesinol and secoisolariciresinol), or other compounds play the primary role. Isoflavones and lignans are thought to exert their effects through diverse mechanisms, including the modulation of insulin secretion in the pancreas and antioxidant actions. Each plant offers unique phytochemicals, contributing to a diverse spectrum of bioactive compounds that may aid in the management of obesity. This expanding field of research highlights the importance of phytoestrogens in developing comprehensive dietary and therapeutic strategies for obesity management, enhancing our understanding of their role in metabolic health.
Potential contraindications: While there is generally no direct contraindication, individuals taking obesity medications such as orlistat, phentermine-topiramate, bupropion-naltrexone, or liraglutide should be cautious of potential interactions with phytoestrogen-containing products.
3.3 Cardiovascular diseases
The role of phytoestrogens in cardiovascular disease prevention is gaining increasing attention due to their varied and significant effects on heart health. These naturally occurring compounds, found in a variety of plants, have been linked to multiple benefits that collectively reduce the risk of cardiovascular diseases. Isoflavones from soybeans, particularly genistein and daidzein, have been extensively studied for their cardiovascular benefits. Genistein is known to improve endothelial function, which is crucial for maintaining the health and elasticity of blood vessels. This improvement in endothelial function can lead to better blood flow and reduced risk of arterial blockages. Genistein has also been observed to lower LDL cholesterol levels, which is essential in preventing the buildup of plaques in the arteries, a major risk factor for heart disease. Lignans found in flaxseeds are another group of phytoestrogens with cardiovascular benefits. These compounds have been linked to improved blood pressure regulation and healthier lipid profiles. By influencing these factors, lignans can significantly reduce the risk of hypertension and atherosclerosis, both of which are key contributors to cardiovascular disease.
Genistein has been the subject of numerous investigations. Studies have indicated that genistein may improve endothelial function, a critical factor in maintaining healthy blood vessels [27]. This property of genistein, along with its potential to reduce LDL cholesterol levels, underscores its significance in cardiovascular health. Flaxseeds (Linum usitatissimum L.), a potent source of lignans, like secoisolariciresinol diglucoside and matairesinol, contribute to the multifaceted approach in mitigating cardiovascular risks [28]. Lignans from flaxseeds may contribute to blood pressure regulation. Additionally, lignans have been associated with favorable effects on lipid profiles, further solidifying their role in cardiovascular health [28]. Red clover (Trifolium pratense L.), known for its isoflavones formononetin and biochanin A, provides another avenue in the pursuit of cardiovascular wellness. Research demonstrated that red clover isoflavones may lead to modest reductions in LDL cholesterol levels, a pivotal factor in preventing atherosclerosis [29]. Hops (Humulus lupulus L.), a plant rich in the compound xanthohumol, shows promise in cardiovascular health. Studies suggest that xanthohumol may contribute to reducing LDL cholesterol oxidation, an essential step in preventing atherosclerosis [30, 31]. Pomegranate (Punica granatum), known for its rich content of ellagitannins, offers potential benefits for cardiovascular health [32]. Research indicated that pomegranate polyphenols may contribute to the inhibition of LDL cholesterol oxidation, a crucial step in preventing plaque formation [33].
Additionally, Black cohosh (Actaea racemosa L.), containing triterpene glycosides, like cimicifugoside and actein, may also play a role in cardiovascular health [34]. Though less studied in this context, emerging research suggests that compounds within black cohosh may contribute to cardiovascular wellness through their diverse biological activities [35]. Alfalfa (Medicago sativa L.), a plant rich in coumestans, like medicagol, may contribute to cardiovascular health [36].
The diverse range of phytoestrogens, each with unique properties, collectively contribute to heart health. They work by improving endothelial function, lowering harmful cholesterol levels, reducing blood pressure, and preventing the oxidation of LDL cholesterol. Incorporating phytoestrogen-rich foods into the diet could be a valuable strategy for reducing the risk of cardiovascular diseases.
Potential Contraindications: Potential interactions and contraindications exist between certain cardiovascular medications and phytoestrogens. For instance, warfarin showed interaction with phytoestrogen-rich foods. Grapefruit juice, containing phytoestrogens, can interact with statins like atorvastatin and simvastatin. Beta-blockers such as metoprolol and atenolol could be affected by the mild blood pressure-lowering effects of isoflavones in soy. While there are no direct contraindications, individuals on antihypertensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers need to be mindful of potential interactions when consuming phytoestrogen-rich foods, monitoring blood pressure as needed.
3.4 Osteoporosis
Osteoporosis is a prevalent bone disease characterized by reduced bone mass and deteriorating bone tissue, leading to increased fracture risk [37]. This condition is particularly common among postmenopausal women due to the decrease in estrogen levels, a hormone vital for bone health [38]. Phytoestrogens have shown potential in mitigating the risk and progression of osteoporosis, primarily due to their estrogen-like effects. The mechanism behind the beneficial effects of phytoestrogens on bone health is primarily linked to their ability to bind to estrogen receptors in the body. This binding can help compensate for the decreased estrogen levels in postmenopausal women, a key factor in the development of osteoporosis. Phytoestrogens can modulate the activity of osteoclasts (cells that break down bone tissue) and osteoblasts (cells that build new bone), helping to maintain a balance in bone remodeling. Moreover, phytoestrogens have antioxidant properties (explained in the later section of this chapter), which may help protect bone tissue from oxidative stress and inflammation, further contributing to their osteoprotective effects.
Isoflavones are the most studied phytoestrogens in the context of bone health. They have been shown to positively influence bone mineral density (BMD). Studies suggest that isoflavones like genistein and daidzein may help in preserving BMD in postmenopausal women, potentially reducing the risk of osteoporotic fractures [39]. Lignans are abundant in flaxseeds, sesame seeds, and whole grains. They are converted into enterolignans by intestinal bacteria, which then exert estrogenic effects. Research indicates that lignan intake is associated with improved bone turnover markers and could be beneficial in maintaining bone density, particularly in postmenopausal women [40]. Coumestans, less common but present in foods like alfalfa and clover, also exhibit estrogenic properties and may play a role in bone health, although more research is needed in this area [41].
In addition to flaxseeds and sesame seeds, chia seeds (Salvia hispanica) represent another notable source of lignans. The presence of alpha-linolenic acid, an omega-3 fatty acid, in chia seeds further complements their potential in supporting bone health. Omega-3 fatty acids have been associated with anti-inflammatory effects, which can contribute to a favorable bone environment [42]. Hops (Humulus lupulus L.) has also shown promise in bone health. Studies suggest that xanthohumol may have a protective effect on bone density, making it an intriguing subject for further investigation [43]. Red clover (Trifolium pratense L.) may have a positive impact on bone health in postmenopausal women [44].
It is important to note that while phytoestrogens, including lignans, present promising potential in supporting bone health, they are most effective when integrated into a comprehensive approach to osteoporosis management. This approach includes a balanced diet rich in essential nutrients for bone health, weight-bearing exercises, and, when necessary, conventional medical interventions. The diverse array of plants and their corresponding phytoestrogen compounds offer intriguing possibilities for the preservation of bone integrity. Lignans from flaxseeds, sesame seeds, and chia seeds, along with compounds from hops and red clover, exemplify nature’s potential contributions to the fight against osteoporosis.
Potential Contraindications: Potential interactions and contraindications may exist between certain osteoporosis medications and phytoestrogens. Bisphosphonates like alendronate and risedronate may be affected by excessive calcium intake from soy, potentially impacting medication absorption. Selective estrogen receptor modulators (SERMs) like raloxifene, which have estrogenic effects, may interact with phytoestrogens, possibly leading to additive estrogenic effects on bone health.
Phytoestrogens, derived from plants, possess robust antioxidant properties. They excel in neutralizing harmful free radicals, inhibiting lipid peroxidation, and bolstering the body’s enzymatic and nonenzymatic antioxidant defenses. These actions collectively mitigate oxidative stress, a critical factor in metabolic diseases [5].
4.1 Mechanisms of antioxidant action
Phytoestrogens possess powerful antioxidant properties, which stem from their ability to scavenge free radicals, inhibit lipid peroxidation, and modulate enzymatic antioxidant defenses. These actions collectively contribute to a reduction in oxidative stress.
The antioxidant actions of phytoestrogens are multifaceted, involving several key mechanisms:
4.1.1 Free radical scavenging
Phytoestrogens are adept at scavenging free radicals, highly reactive molecules that can cause cellular damage. By neutralizing these radicals, phytoestrogens help prevent the chain reactions that lead to oxidative stress.
4.1.2 Inhibition of lipid peroxidation
Lipid peroxidation is a destructive process where free radicals attack lipids in cell membranes, leading to cellular dysfunction. Phytoestrogens, through their chemical structure and reactivity, have the capacity to interrupt this chain of events, preserving cellular integrity.
4.1.3 Modulation of enzymatic antioxidant defenses
Phytoestrogens can influence the activity of enzymatic antioxidants within cells. These enzymes, such as superoxide dismutase and catalase, are crucial in neutralizing harmful reactive oxygen species (ROS). By enhancing their activity, phytoestrogens bolster the cell’s defense against oxidative damage.
4.1.4 Enhancement of nonenzymatic antioxidants
In addition to affecting enzymatic defenses, phytoestrogens can boost the levels of nonenzymatic antioxidants, such as glutathione and vitamins C and E. These molecules play pivotal roles in neutralizing ROS and preventing cellular harm.
Notably, different phytoestrogen compounds exhibit varying degrees of antioxidant efficacy. For instance, isoflavones, prevalent in soybeans and legumes, are recognized for their potent antioxidant activity [45]. Genistein has been extensively studied for its ability to quench free radicals and protect cells from oxidative damage [46]. Lignans, found abundantly in flaxseeds, sesame seeds, and whole grains, also contribute significantly to antioxidant defenses [47]. Their structural attributes allow them to intercept free radicals and impede oxidative stress. Coumestans, present in various legumes and sprouts, possess antioxidant capabilities [48]. Compounds like coumestrol have demonstrated the capacity to mitigate oxidative damage by neutralizing free radicals [49]. Stilbenes, such as resveratrol found in red grapes, berries, and peanuts, are recognized for their potent antioxidant effects [50]. They are particularly adept at inhibiting lipid peroxidation and preserving cellular integrity.
Thus, the antioxidant roles of phytoestrogens represent a crucial aspect of their potential health benefits. Their ability to scavenge free radicals, inhibit lipid peroxidation and modulate enzymatic and nonenzymatic antioxidant defenses collectively contribute to reducing oxidative stress. Understanding these mechanisms provides valuable insights into the potential applications of phytoestrogens in combating metabolic diseases and promoting overall health.
4.2 Roles of phytoestrogen’s antioxidant activity in metabolic diseases
The antioxidant capabilities of phytoestrogens extend their benefits beyond mere hormonal mimicry, playing a vital role in combating metabolic diseases where oxidative stress is a key perpetrator [51, 52]. This stress, characterized by an overabundance of reactive oxygen species (ROS), is a critical factor in diseases like type 2 diabetes, obesity, cardiovascular diseases, and osteoporosis.
In type 2 diabetes, phytoestrogens, especially isoflavones from soybeans, show promise in enhancing insulin sensitivity and improving glucose metabolism [53]. They achieve this by counteracting oxidative stress through the neutralization of free radicals and the inhibition of lipid peroxidation. Genistein, in particular, stands out for its effectiveness in protecting pancreatic beta cells, which are crucial for insulin production [54].
In the realm of obesity, a condition deeply intertwined with oxidative stress, phytoestrogens demonstrate a capability to modulate fat metabolism and suppress adipogenesis [55]. This effect is particularly significant in maintaining the integrity of cells in adipose tissue. The antioxidant properties of compounds like isoflavones, lignans from sources like flaxseeds, and stilbenes from red grapes contribute to these protective effects [56].
Regarding cardiovascular diseases, oxidative stress is a well-known contributor. Phytoestrogens, through their antioxidant actions, scavenge free radicals, inhibit lipid peroxidation, and boost enzymatic antioxidant defenses, offering a multipronged shield against cardiovascular complications. Specific phytoestrogens like isoflavones from soybeans, resveratrol from red grapes, and epigallocatechin gallate (EGCG) from green tea have been shown to be particularly effective. These compounds aid in lowering blood pressure, reducing levels of harmful LDL cholesterol, and enhancing endothelial function, which is pivotal for vascular health [57, 58].
For osteoporosis, characterized by reduced bone density and increased fracture risk, phytoestrogens, particularly lignans found in flaxseeds and sesame seeds, are of great interest. They safeguard bone health by protecting bone cells against oxidative damage. Secoisolariciresinol, a prominent lignan, is notably effective in this regard [59, 60].
Overall, the antioxidant activity of phytoestrogens offers a comprehensive approach to mitigating oxidative stress, a central factor in various metabolic diseases. By neutralizing harmful free radicals, preventing lipid peroxidation, and enhancing the body’s own antioxidant defenses, phytoestrogens present a natural and multifaceted strategy to address oxidative damage. This highlights the potential of incorporating phytoestrogen-rich foods and supplements as valuable components in the prevention and management of these metabolic diseases.
Phytoestrogens, in the context of metabolic diseases, reveals a fascinating spectrum of natural compounds with significant health benefits. These substances, structurally similar to estrogen, exhibit both estrogenic and antioxidant activities, presenting themselves as potential therapeutic agents in various metabolic disorders. This chapter highlighted the roles of different phytoestrogens-isoflavones, lignans, and coumestans, in combating metabolic diseases. Their ability to mimic estrogenic activity and interact with estrogen receptors offers promising therapeutic avenues in conditions like type 2 diabetes, obesity, cardiovascular diseases, and osteoporosis. For instance, isoflavones in type 2 diabetes improve insulin sensitivity, while lignans in osteoporosis enhance bone mineral density.
The antioxidant capabilities of phytoestrogens further broaden their therapeutic scope. By scavenging free radicals, inhibiting lipid peroxidation, and bolstering enzymatic antioxidant defenses, they offer protection against oxidative stress, a common factor in many metabolic diseases. Beyond these, the exploration of a variety of phytoestrogen-rich plants like grapes, berries, green tea, and alfalfa showcases the vast potential of these compounds in metabolic health. Thus, phytoestrogens represent a burgeoning field in the management of metabolic diseases. Their unique properties and diverse mechanisms of action open up new possibilities for integrating natural approaches with conventional medical treatments. As research advances, the role of phytoestrogens in metabolic health is set to become increasingly significant, offering a harmonious blend of nature and science in combating these conditions.
The authors are thankful to the Ministry of Health (MOH) and the National Medical Research Council (NMRC), Singapore, for financial assistance grant number NMRC/OFYIRG/0002/2016 and MOH-000319 (MOH-OFIRG19may-0002), Khoo Bridge Funding Award (DUKE-NUS-KBRFA/2023/0075), and Duke/Duke-NUS Collaboration Pilot Project award (RECA(Pilot)/2022/0060) to BKS; NMRC/OFYIRG/077/2018 to MT.
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Written By
Manish Kumar Verma, Brijesh Kumar Singh and Madhulika Tripathi
Submitted: 22 January 2024Reviewed: 24 January 2024Published: 29 February 2024
Open access peer-reviewed chapter - ONLINE FIRST
