2. Health benefit of soy or soy products
Soy products have been considered as great source of protein for many decades. Japanese, in particular, eat a soy-based diet. Japanese monks eat soy products as their main protein source. They are known to live longer and have lower rates of chronic diseases. Because soybeans contain practically no starch, soybeans are an important part of a diabetic diet. Soybeans are 1) rich in protein (
Many studies have shown that American and European males have a ten-fold increase in the risk of prostate cancer development as compared with East Asian countries. The observed difference prevalence of prostate cancers is considered due, in part, to difference in soy consumption. Some studies indicated that isoflavones found in soybeans contribute to the risk reduction of prostate cancer. Although there is a lack of unequivocal evidences that consuming soy as an adult may reduce the risk of breast cancer, several researches have reported that consuming soy products as a teenager may help reduce breast cancer risk as an adult. Some medical research has determined that ingredients of soybeans may help reduce the risk of colon cancer and heart diseases. The dramatic increase in soy products is due largely to the fact that the US FDA approved soy products as an official cholesterol-lowering food, along with other heart and health benefits due to the evidence that soy product intake is correlated with significant decreases in serum cholesterol, low-density lipoprotein (LDL, bad cholesterol) and triglycerides. Although a significant health benefit has been observed in people with a high soy intake (
3. Chemical composition of soybeans
Remarkably, seeds of soy contain very high levels of protein, carbohydrate conjugates, fatty acids (soybean oil), amino acids, and inorganic materials (minerals). Among these soybean components, protein and fatty acid content account for about 40% and 20%, respectively. The remaining components consist of carbohydrate conjugates, inorganic constituents, and the minor components of biologically interesting small molecules (molecules highlighted below). Thus, soybeans constitute important nutritional components. Soybeans are considered to be a good substituents of protein (essential amino acids), amongst other major vegetables, for animal products. This chapter reviews
Isoflavones (a subgroup of flavonoids) are known to be highly potent antioxidants (Fig.1). As stated above, the consumption of soy products has many health benefits, including protection against breast cancer, prostate cancer, menopausal symptoms, heart disease and osteoporosis. Many of the health benefits of soy are derived from its isoflavones. Isoflavones are produced
Genistein is found in a number of plants including soybeans, lupin, fava beans, kudzu, psoralea, and coffee. Genistein is the most discussed phytoestrogenic substance, because it is very well represented in soybeans. Genistein influences several targets in living cells. Due to its structural similarity to estrogen (i.e. 17β-estradiol, Fig. 2), genistein can bind to estrogen receptors. Genistein shows much higher affinity toward estrogen receptor β (ERβ) than toward estrogen receptor α (ERα).
Estrogen is a key regulator of growth and differentiation in a broad range of tissues, including the reproductive (genital) system, mammary gland, central nervous and skeletal systems. Estrogen is also known to be involved in breast and endometrial cancers. To date, two key conclusions can be highlighted from the significant number of studies on the specific roles of the two receptor subtypes in diverse estrogen target tissues. ERα and ERβ have different transcriptional activities in certain cell-type, which help to explain some of the major differences in their tissue-specific biological actions. Both ERs are widely expressed in different tissue types, however, there are some distinct differences in their expression patters. The ERα is found in the inner membrane of the uterus (endometrium) and breast cancer cells. On the other hand, ERβ is found in kidney, brain, bone, heart, lung, intestinal mucosa, prostate, and endothelial cells. Unwanted effects are generally mediated through ERα. Roles of ERβ have been the subjects of interest in human cancer researches. Recent studies have shown that ERβ is lost in majority of breast tumors and thus
In the 1960’s, many researches regarding the physiological effects of genistein were limited to its estrogenic activity. Genistein have also been shown to possess antifungal activities (Weidernbörner, et al. 1989), antiangiogenic effects (blocking formation of new blood vessels), and may block the uncontrolled cell growth associated with cancer, most likely by inhibiting the activity of substances in the body that regulate cell division and cell growth factors. Various studies have found moderate doses of genistein to have inhibitory effects on cancers of the prostate, cervical, brain, breast, and colon. Additionally it has been shown that genistein makes some cells more sensitive to radio-therapy. Genistein has shown a protein tyrosine kinase inhibitory activity. Tyrosine kinases are implicated in almost all cell growth and proliferation signal cascades. Genistatin’s inhibition of DNA topoisomerase II also plays an important role in the cytotoxic activity of genistein.
Daidzein is also present a number of plants. Soy foods typically contain more genistein than daidzein. Structurally, daidzein lacks the 5-hroxy group of genistein (Fig. 1). Genistein and daidzein can transfer across the human placenta at environmentally relevant levels and their influence to early puberty in children is unknown.
Glycitein is unique in that it is an isoflavone found in soy with a methoxy group. Methylated isoflavones have been shown to be more bioavailable and biologically stable than non-methylated isoflavones. Glycitein accounts for 5-10% of the total isoflavones in soy food products. Glycitein shows a weak estrogenic activity, comparable to that of the other soy isoflavones.
Formononetin is an
3.1.5. Biochanin A
Biochanin A is an
Equol has the 3
3.1.7. Isoflavone glycosides
Isoflavones generally exist as aglycones (Fig. 1) and their glycoside forms. Isoflavone glycosides isolated from soybeans are β-glucosidated at C7-position of isoflavone core structure. Soybeans are known to contain daidzein, glycitin, 6”-acetylgenistin, 6”-acetyldaizin (Waltz, 1931; Naim, et al. 1973; Ohta, et al. 1979). Later, malonylglycosides (6"-
As describe above, biological effects of aglycones of isoflavone glycosides found in soybeans have been of great interest in food science, food technology, nutrition and dietary supplements, and disease prevention or treatment. Due to the fact that isoflavones in soybeans are conjugated almost exclusively to sugars, thus, understanding of the mechanism of intestinal absorption of isoflavones in humans is an important subject. Evidence from intestinal perfusion and
3.1.8. Controversial effect of soy isoflavones
Recently, a lot of articles regarding the negative aspects of soy have been published. However, several controversy reports about the adverse effects are always not clear. This may be due to the lack of understanding of metabolism and bioavailability of isoflavones in soy products. Some studies concluded that the bioavailability and pharmacokinetics of isoflavones are significantly influenced by type of soy products. Examples of adverse effects of isoflavones are that genistein 1) increased the rate of proliferation of estrogen-dependent breast cancer
3.2. Phytic acid
Phytic acid [hexakisphosphate (IP6)) or phytate] is present in the brans and hulls of most grains, beans, nuts, and seeds. Rich sources of phytic acid are wheat bran and flaxseed. Phytic acid is inositol hexaphosphate, and thus it is highly charged, which provided chelative (or binding) properties. Phytic acid binds to minerals and metals. Phytate is not digestible to humans or nonruminant animals. The chelated forms of phytic acid with Zn, Ca, and Mg make them impermeable molecules through cell membranes. Phytic acid blocks the body's uptake of essential minerals such as magnesium, calcium, iron and especially zinc. On the other hand, phytic acid is known to be an antioxidant as well as helpful in eradication of heavy metals and other toxic cation species from the body.
3.3. Soybean lipids
Lipids are broadly defined as hydrophobic or amphiphilic molecules. Lipids include fatty acids, sterols, lipid-soluble vitamins (vitamins A, D, E and K), glycerolipids, phospholipids, glycolipids, and sphingoglycolipid. Soybeans contain 82% of triacylglycerol, 13% of phospholipids, about 1% of sterols, and 4% of unsaturated and saturated fatty acids in a total lipid extracted with chloroform-methanol (2/1). Phospholipid composition in a soybean lipid extract is phosphatidylcholine (42%), phosphatidylethanolamine (30%), phosphatidylinositol and phosphatidylserine (20%), lysophosphatidylcholine (1%), sphingomyeline (0.6%), phosphatidic acid and others, respectively (Takagi et al. 1985).
Lipids remain an important research subject because of associations between consumption of lipids and the incidence of some chronic conditions including coronary artery disease, diabetes, cancer and obesity. Dietary lipids (or fats) serve multiple purposes. The importance of antioxidant ability of unsaturated fatty acids including β-carotene in the prevention of cardiovascular disease as well as many cancers is being increasingly recognised. Although saturated fatty acids are generally considered cholesterolemic, it is now evident that the effect of some fatty acids on blood lipids and lipoproteins suggest that the major dietary fats containing in some food products (i.e. soybeans or palm oils) do not raise plasma total fatty acids and LDL cholesterol levels. In recent times, adverse health concerns from the consumption of trans fatty acids arising from hydrogenation of oils and fats have been the subject of much discussion and controversy.
3.3.1. Fatty acids and soybean oil
Soybean oil is rich in polyunsaturated fatty acids, including the two essential fatty acids, linoleic and linolenic, that are not produced in the human body. Linoleic and linolenic acids aid the body's absorption of vital nutrients and are required for human health.
In many applications, the higher saturate oils have been replaced with partially hydrogenated vegetable oils. Partially hydrogenated oils make the oil more stable and more resistant to air oxidation. Saturated fatty acids are more difficult to digest than unsaturated fatty acids and are seldom used for food product industry applications. Nature makes most mono- and polyunsaturated fatty acids in the
3.3.2. Soy sterol
Soybeans contain plant sterols, β-sitosterol, β-sitostarol, campesterol, campestanol, brassicasterol, stigmasterol, and Δ5-avenasterol, and cholesterol (Fig. 6). Plant sterols are natural dietary components, and known to have serum cholesterol-lowering properties. The lowing of serum cholesterol by plant sterols is believed to be the result of an inhibition of cholesterol absorption in small intestine. Several studies suggested that unsaturated or saturated plant sterols showed different effects on cholesterol absorption and sterol excretion (Normén et al. 2007).
Glycerolipids are composed of mono-, di- and tri-substituted glycerols. In these compounds, the three hydroxy groups of glycerol are esterified (triacylglycerols) or one of hydroxy group forms the ether linkage. Subclasses of glycerolipids are represented by glycosyl glycerols and glycerophospholipids. Glycerophospholipids are subdivided into distinct classes which are characterized by the presence of one or more sugar or phosphate residues (i.e. phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol, and phosphatidyl serine).
Soybeans contain a wide variety of triacylglyceroles, however LC-MS analyses revealed that fatty acids incorporated in soy triacylglycerols are stearic acid, palmitic acid, oleic acid, linoleic acid, and linolenic acid (Neff et al. 1995). Fatty acids in soybeans are considered to be stored as triacylglycerides.
Lecithin can easily be extracted from soybeans (or egg yolk) and soy lecithin is an additive found in many everyday foods (Fig. 5). It has low solubility in water. Due to its amphipathic characteristic, lecithin phospholipids can form either liposomes, bilayer sheets, micelles, or lamellar structures in aqueous solution. In cooking, it is sometimes used as an emulsifier and to prevent sticking (for example, in non-stick cooking spray) and or as a stabilizer in various food applications. Lecithin has been a popular supplement because it’s high choline (
Phosphatidylinositol (PI) is classified as a glycerophospholipid that contains a glycerol backbone, two non-polar fatty acid tails, a phosphate group substituted with an inositol (
Sphingolipids are structural components of eukaryotic cell membranes. A large number of recent reports have indicated that sphingolipid are involved in a number of important regulatory processes in cell development. Cerebrosides (monoglycosylceramide) is the common name for a group of glycosphingolipids.
Soya-cerebroside (Fig. 5) is a glucosylceramide isolated from soybeans, exhibited a Ca2+-binding activity. The basic structure of soya-cerebroside II including the absolute stereochemistries of (
Sphingomyelin is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It consists of phosphorylcholine and ceramide (Fig.5). In humans, sphingomyelin represents ~85% of all sphingolipids. On the other hand, only 0.6% of sphingomyelin was found in a total phospholipid isolated from soybeans (Takagi, et al. 1985). The accumulation of sphingomyelin (i.e. Niemann-Pick Disease) in brain causes irreversible neurological damage. Sphingomyelin in food products is not bioavailable, and thus the accumulation of sphingomyelin in human body is not considered possible by sphingomyelin containing food intake.
3.3.6. Vitamin K
Vitamin K is a lipid-soluble essential vitamin that is stable to air but susceptible to air under sunlight. The "K" is derived from the German word “koagulation”. Natural forms of vitamin K, vitamin K1 (phylloquinone) and vitamin K2 (menaquinone), exist in the human liver and other tissues at very low concentrations; vitamin K1 concentrates in the liver while vitamin K2 is well distributed to other tissues (Fig.7). Vitamin K1 is derived from dietary intake and vitamin K2 is produced by intestinal bacteria. Thus, vitamin K is not listed among the essential vitamins. Human get most of our dietary vitamin K in the form of phylloquinone (biosynthesized by plants). In prokaryotes, especially in Gram-positive bacteria, vitamin K2 will transfer two electrons in a process of aerobic or anaerobic respiration (electron transport systems). Respiration occurs in the cell membrane of prokaryotic cells. Electron donors will,with the help of another enzyme, transfer two electrons to vitamin K2. Vitamin K2, with the help of another enzyme, will in turn transfer these two electrons to an electron acceptor.
One tablespoon of soybean oil contains about 25 μg of vitamin K1 (about 47 μg of vitamin K1 in 100g of soybeans). Green leafy vegetables and some vegetable oils are major contributors of dietary vitamin K. Nattō, a fermented Japanese soybean product, contains large amounts (approximately 870 μg per 100 grams of nattō) of vitamin K2. Vitamin K2 is known to be more effective than vitamin K1 with respect to osteroclastogenesis, hypocholesterolemic effects, and ability to slow atherosclerotic progression. To date, no adverse effects have been reported for higher levels of vitamin K intake from food and/or supplements, there are no documented toxicity symptoms for vitamin K.
In the human diet, carotenoids have been shown to have antioxidant activity which may help to prevent certain kinds of cancers, arthritis and atherosclerosis. β-Carotene is a precursor of vitamin A (retinal) which is biosynthesized
3.3.8. Vitamin E
Vitamin E is a lipid-soluble compound and a family of eight related compounds that includes both tocopherols and tocotrienols. α-Tocopherol is most abundant in foods and also dominates in vitamin E supplements; the other leading types are β-, γ-, and δ-tocopherol. α-Tocopherol has become synonymous with vitamin E, and vitamin E is one of the most popular supplements. Vitamin E has antioxidant activities that stop the production of reactive oxygen species formed when unsaturated fatty acids undergo oxidations. Soybeans and corns contain γ-tocopherol (about 12.0 mg of γ-tocopherol in 100g of total soy lipids) (Fig. 5), while α-tocopherol is found in olive oil.
3.3.9. Vitamin D2 (Ergocalciferol)
There are only a few food sources (fish, liver, and egg yolk) of vitamin D. These are many fortified foods (i.e. milk, soy drinks, orange juice and margarine) that contain vitamin D. Ergosterol, called provitamin D2, is found in ergot, yeast, and other fungi. It is converted to vitamin D2 (ergocalciferol) upon irradiation by ultraviolet (UV) light or electronic bombardment (Scheme 2), whereas, vitamin D3 (cholecalciferol) is normally synthesized in the human skin from 7-dehydrocholesterol. Vitamins D2 and D3 are about equal in activity in all mammals (some literatures described that vitamin D3 is slightly less bioactive). Deficiency of vitamin D can result in rickets (a softening of bones) in children and osteomalacia in adults. The relationship between ergosterol content in soybeans or soybean oils and soybean fungi was studied. For an example, in the studies of soybeans inoculated with spores of
3.4. Soy phytoalexins
Phytoalexins are antimicrobial substances synthesized by plants that accumulate rapidly at areas of pathogen infection. They are, in general, broad spectrum inhibitors and structurally diverse molecules have been isolated from different plant species. Phytoalexins are known to inhibit bacterial or fungus cell wall biosynthesis, or delay maturation, or disrupt metabolism. To date, several soy phytoalexins have been reported. 6a-Hydroxyphaseollin was the first structurally defined phytoalexin isolated from fungal infected soybeans. Several other hydroxypterocarpan (benzopyrano-furanobenzenes) derivatives are biosynthesized as phytoalexins by soybean tissues on treatment with a variety of biotic or abiotic agents. Glyceollins are a family of pterocarpan found in the Fabaceae family including activated soy. They are biosynthesized from the isoflavone, daidzein (Fig. 1)
Coumestrol is classically categorized as phytoestrogens because this molecule binds to the estrogen receptor (ER). Coumesterol is originally isolated from alfalfa (Bikoff et al. 1957), but later soybeans and clover contain the highest concentrations of this molecule. Biosynthesis of coumestrol in soy is proposed based on the feeding experiments of labeled precursors to a coumestrol producing bacteria (Berlin et al. 1972). As illustrated in Scheme 4, the isoflavone, daidzein is reduced to form 2’-hydroxy-2,3-dihydrodaidzein which undergoes intramolecular condensation to yield 3,9-dihydroxypterocarp-6a-en. Biological oxidation of the dihydroxypterocarpen furnishes coumestrol.
Coumestrol has less estrogen activities than estrogen and therefore may reduce the risk of developing breast or prostate cancer in humans by preventing estradiol binding to estrogen receptor (ER). Coumestrol was reported to inhibit the enzymes involved in the biosynthesis of steroid hormone (aromatase and hydroxysteroid dehydrogenase), and inhibition of these enzymes results in the modulation of hormone production.
Saponins are amphipathic glycosides grouped phenomenologically by the formation of soap-like froth when shaken in aqueous solutions. Structurally, saponins contain one or more glycoside moieties combined with a lipophilic triterpene derivative. Many health benefits of soybeans are believed to be attributed to their Saponins. Many soy products contain high levels of saponins. Raw soybeans contain between 2 and 5 g saponins per 100 g. Soy saponins are divided in two groups; group A saponins have and undesirable astringent taste, and group B saponins have the health promoting properties.
The blood cholesterol-lowering properties of dietary saponins are of particular interest in human nutrition. Saponins bind cholesterol and bile acids in the gut. Cancer cells have more cholesterol-type compounds in their membranes than normal cells. Soy saponins can bind cholesterol
3.7. Lectins and hemagglutinins
Lectins are plant derived proteins which are capable of binding to carbohydrate moieties of complex glycoconjugates but do not possess immunoglobulin nature. They typically agglutinate certain animal cells and/or precipitate glycoconjugates. Many members of the lectinic protein family agglutinate red blood cells. This particular nature of lectinic proteins is classified into hemagglutinin. Lectins are stable proteins that do not degrade easily. For examples, some lectins are resistant to stomach acid and digestive enzymes. Unfermented soy products contain high levels of lectins/hemagglutinins. Hemagglutinin renders red blood cells unable to absorb oxygen. However, the soybean fermentation process deactivates soya hemagglutinins, and thus the amounts of lectins present in soybeans have not been considered to be as potentially toxic components. On the other hand, some dried bean products may still contain a large amount of active lectins. These lectins are believed to trigger allergic reactions or toxic reactions in a person’s body. Person’s lectin sensitivity is largely due to 1) genetics, 2) a failure of mucosal immunity (secretory IgA), and 3) bacterial or viral infections that damage human cells, making human body susceeptable to lectin antibody/antigen reactions.
3.8. Soy toxins
Soy contains several naturally occurring compounds that are toxic to humans and animals. The best known of the soy toxins is the trypsin (a serine protease found in the digestive system) inhibitors.
3.9. Water-soluble vitamins
Soybeans are not considered to be very rich sources of any particular vitamin, but they contain a wide variety of vitamins and do contribute to an overall nutritional well-being. Lipid-soluble vitamins (vitamin K, E, D and carotene) in soybeans are discussed above. The water-soluble vitamins in soybeans are thiamine, riboflavin, niacin, pantothenic acid, biotin, folic acid, inositol, choline, and vitamin C. Vitamin B6 was also reported to contain in soybeans. Thus, soy includes essential vitamins except for vitamin B12 and E. However, soy contains a vitamin E precursor, carotene. Numerous studies have been conducted over the past decades on the relative distribution and concentrations of these vitamins in different portion of soy. The cotyledons contain notably greater amount of all water soluble soy vitamins than those in the hypocotyl. The quantity of all vitamins except thiamine increases through germination (Wai et al., 1947).
This chapter summarizes structures of biological active molecules isolated from soy, and their biological activities are briefly reviewed. Since the discovery of soybeans as rich source of protein and oil in 1904, a numerous number of experimental data have been accumulated on chemistry and biochemistry of phytochemicals isolated from soy and soy products. To date, a wide variety of organic compounds have been characterized from soy. The interest of structure elucidation studies of bioactive molecules in soy was to obtain insight into correlation between the reported health benefits, which are associated with soy intake, and soy phytochemicals. Thus, many structural studies on soy have not aimed to discover novel molecules, albeit these efforts resulted in discovery of complex soyasaponins (Fig. 9.). The consumption of soy products has many health benefits, including protection against breast cancer, prostate cancer, menopausal symptoms, heart disease and osteoporosis. These health benefits of soy are believed to be due in part to phytoestrogenic activity of isoflavones, which are stored as glucosyl- and malonyl-glucose conjugates in soybeans. Isoflavon-glucosyl conjugates show very poor oral bioavailability. Recently, the negative aspects of soy have been reported (3.1.8). However, the controversy reports about the adverse effects of soy are not clear. This may be due to the lack of understanding of metabolism and bioavailability of isoflavone-glucosyl conjugates in soy. Some researchers concluded that there is little clinical evidence to suggest that isoflavones will cause the adverse effects (e.g. breast cancer risk in healthy women). It is important to note that all phytochemicals isolated from soy show an array of weak biological activities, and thus, normal consumption of foods that contain these phytochemicals should not provide sufficient amounts to elicit a visible physiological response in humans in short-time clinical researches.
Unfermented soy products contain high levels of lectins/hemagglutinins, and very low level of soy toxins (protease inhibitors). Most of these proteins will be deactivated through food processing. Remarkably, seeds of soy contain very high levels of protein, carbohydrate conjugates, oil, and minerals. On the other hand, remaining components discussed in this chapter can be isolated minute quantities from soybeans, however, a wide range of health benefit of soy phytochemicals (lipids, phytoestrogens, soy sterols, vitamins, soyasaponins) contributes to the overall nutritional well-being of humans.
I would like to thank Emeritus Professor Isao Kitagawa for valuable discussions for this document.