PROTECTIVE AND NORMALIZING BENEFITS OF SOY:
CLINICAL CONSIDERATIONS
Joan Friedrich, Ph.D., CCN
The ArticleSaponins: A Class of Glycolipids
Saponins Safety: Common Concerns
Isoflavones: Protective Micronutrients
Isoflavone Influence on Menstrual Cycles
Gastrointestinal/Hormonal Interactions: Considerations
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Over the last several years, growing attention has been centered on the nutritional ant therapeutic benefits of soybean products. Providing a rich source of protein and nutrients, soy also called phytochemicals. These compounds appear not only to influence physiological functions but also to provide a broad array of protective health benefits. Due to its tremendous potential for clinical application, several major health organizations including the National Cancer Institute (NCI) are investigating the use of soy and phytochemical rich plant foods.
An analysis of soy illustrates that it contains many highly effective micronutrient compounds; each providing distinctive therapeutic benefits. Among the most prominent of these active ingredients include saponins, isoflavones, phytic acid (inositol hexaphosphate), lighans, protease inhibitors and phytosterols and phenolic acid. This paper will provide an overview of these factors.
I. Saponins: A Class of Glycolipids
Saponins are complex glycosidic compounds primarily present in a diverse array of edible and inedible plants . Soybeans however, are one of the major sources of glycosidic compounds found in the human food supply.
Although soy contains various other glycolipids (e.g.: steryl glucosides, esterified steryl glucosides), saponins are one of the most investigated of these fatty acid glycolipids .
Linked to one or more sugar molecules, saponins consist of a steroid or triterpene group (the aglycone) and have characteristic surface activity . A detergent action arises from sapping due to its water-soluble carbohydrate molecules being mixed with its fat-soluble sapogenin portion.
Structurally saponins resemble cholesterol and have been speculated that it is possible that binding of saponins to the hormonal messengers. These messengers may, in turn, have profound effects on gastric and intestinal activities, and perhaps, various activities of the endocrine system.
Characteristically, glycolipid saponins have been associated with cholesterol reduction, an action that occurs primarily though two key mechanisms.
A. Bile excretion
B. Inhibition of cholesterol absorption through the formation of complexes with cholesterol in the gut lumen (6), with the binding of cholesterol appearing to occur within the cell membranes.
In part, some of these actions may concurrently be involved with the soybean fiber, which can effectively absorb bile acids and contribute to cholesterol lowering. In addition, saponin may also alter the function and permeability of intestinal mucosal cells and thereby increase exfoliation and promote profoliation. These activities can also increase fecal cholesterol excretion.
Saponins have also been shown to provide antioxidant and cell-protective properties, immunopotentiating benefits for both humoral and cellular responses, antiviral activity, with suggested inhibitory actions against HIV infection and potential for the treatment of retroviral infection). Other research points to their antibiotic and expectorant actions, and potential anti-carcinogenic benefits.
The anti-cancer benefits of saponins may, to some extent, be linked to their action on cellular surfaces. Since the membranes of some cancer calls contain more cholesterol than normal cell membranes, we may speculate that saponins may actually bind more to cancer cells and thereby participate in their destruction.
Further research supporting the cancer protective properties of saponins suggests that they may also have cytotoxic and growth inhibitory effects on tumor cells, and prevent mutation.
Saponins Safety: Common Concerns
It was once believed that saponins were harmful, probably due to both the toxicity saponin has to fish and cold-blooded-animals and the hemolytic activity that many saponins found in nature appear to possess.
Although saponins are highly toxic if administered intravenously to mammals, oral use in mammals appears to yield low toxicity. This is due to almost complete failure to pass the gut wall and be absorbed into the blood stream. Any reported haemmolytiic activity is also much diminished or lost in the presence of plasma or its constituents.
Since the actual saponin content of soybeans is also rather low and a 75 to 1 protein per saponin ratio exists (in situ). It may be assumed that in the digestive tract the hemolytic activity of the saponin is fully masked by accompanying proteins.
II. Isoflavones: Protective Micronutrients
Soy isoflavones include predominately genistein, secondarily, daidzein and to a far lesser extent, equol, O-desmethylangolensin and their precursors. Influencing hormonal regulation, these components appear to provide a broad array of health benefits.
Isoflavones glycosides appear to offer protection against various male and female hormone related cancers, including those affecting the prostate and breast. The benefits of these phytochemicals may be primarily attributed to their antioxidant content, estrogen and anti-estrogen effects, and anti-cancer properties.
Isoflavones hold prominence as one of the most investigated ingredients of soy. To a large extent, this is because they resemble and act like estrogens in the body. They have been shown to have the ability to compete and interfere with the body’s natural estrogens. By attaching to estrogen receptor sites, isoflavones provide weaker yet effective estrogen activity while blocking potentially harmful natural endogenous estrogens. Studies also indicate that isoflavones administered or by their presence in the diet may also be protective against high levels of synthetic estrogens. Since the structure of isoflavones also resemble the anti-estrogen tomoxifen, their therapeutic use is being investigated for breast cancer prevention.
Genistein, the predominant soy isoflavone, has been shown to provide specific anti-cancer benefits. It has been reported that genistein can inhibit the enzyme tyrosine protein kinase (TPK), a cell growth regulator, most likely at the ATP-binding sites. TPKs are associated with receptors of substances regulating epidermal growth factor, platelet derived growth factor, insulin and insulin-like growth factor. They also show structural similarity with estrogen and progesterone receptors. Other reports indicate that genistein also affects other enzymes involved in the cancer process, inhibits angiogenesis, inhibits cancer-cell growth and prompts cancer cells to differentiate and return to normal cell status.
Daidzein, the second most researched isoflavone, is also receiving broad research attention. The pharmaceutical development of the prescriptive drug Ipriflavone has evolved from this interest. Used to prevent decreases in bone mass in osteoporotic subjects, Ipriflavone has been shown to have a chemical structure similar to isoflavone, while also yielding a daidzein metabolite.
Soy rich in phytoestrogens has also been found to offer protection against coronary heart disease (CHD). Data from a recent study conducted on male and female subjects found that soy protein, which included phytoestrogen portions intact provide greater benefits on lipid profiles than soy with the phytoestrogen extracted or animal protein. Such findings are compatible with cross-cultural studies, which indicated lower rates of CHD in countries with greater soy consumption.
Isoflavone Influence on Menstrual Cycles
In a recent study of premenopausal women with regular ovulatory cycles it was found that the addition of a daily intake of 60 grams of soy protein containing 45 mg of isoflavones (a modest amount compared to the typical Japanese dietary intake of 150-200 mg of isoflavones per day) had various effects. Increased follicular phrase length or delayed menstruation (and increase total cycle length) from as much as one to five days were one of the most significant findings. Despite these chances however, no change in the leutal phase was observed during the soy consumption period.
Since mitotic rate for breast tissue is greatly increased during luteal phase rather that follicular phase, women with shorter cycles are believed to be at a greater risk for breast cancer due to spending proportionally more of their lifetime in the luteal phase.
Concurrent hormonal monitoring revealed that midcycle surges of the gonadotrophins luteinizing hormone (LH) and follicular stimulating hormone (FSH) were also significantly suppressed by soy-protein ingestion. During the follicular phase plasma estradiol concentrations increased and cholesterol concentrations decreased 9.6%. Similar results have been observed in female breast cancer patients taking Tomoxifen.
III. Fatty Acids and Phospholipids
Soy oils and the fat I soy products are low in saturated fat (approximately 15 percent). Fifty percent of the fat in soy oil consists of the essential fatty acid, linoleic acid, while a portion (eight- percent) consists of linolenic acid, Omega-3.
The therapeutic phospholipid content of soy however, is most notably associated with its polyunsaturated phosphatidylcholine (PPC) content. Providing a rich source of nontoxic polyunsaturated-rich choline, PCC fatty acids serve varied functions when incorporated into membranes. These can be summarized as follows:
1. They are high energy, structural and functional elements of all biological membranes.
2. They are indispensable for cellular differentiation, proliferation and regeneration.
3. They maintain and promote biological activity of many membrane-bound proteins and receptors.
4. They play a decisive role for the activity and activation of numerous membrane-located enzymes, such as sodium-potassium ATPase, adenylate cyclase and lipoprotein lipase.
5. They are important for the transport of molecules through membranes.
6. They control membrane-dependent metabolic processes between the intracellular and intercellular space.
7. The polyunsaturated fatty acids content (e.g.: linoleic) are precursors of the cytoprotective prostaglandins and other eicosanoids.
8. As choline and fatty acids donors, they have an influence in certain neurological processes.
9. They emulsify fat in the gastrointestinal tract.
10. They are important emulsifiers in the bile.
11. They codetermine erythocyte and platelet aggregation.
12. They influence immunological reaction on the cellular level.
PCC therefore has broad application as a membrane therapeutic and as an effective agent for various indications including skin disorders (psorisis), neurological diseases, geriatric conditions, lung/respiratory diseases, gastrointestinal inflammation, gestosis, atherosclerosis, hyperlipoproteinemia, liver diseases, fat metabolism and renal disease.
It may therefore be assumed that the high proportion of protective fatty acids from PCC in soy provides yet another important supplementary benefits.
IV. Lignans
Lignans are formed in the gut by the bacterial fermentation of certain dietary fibers containing lignan precursors. These factors have been shown to broadly influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation and angiogenesis. The mammalian lignans, enterolactone and enterodiol for example, are formed from plant precursors by the action of intestinal flora.
Much like the action of isoflavones, lignans possesses estrogen and anti-estrogenic activity. A recent study found that omnivorous women who were either breast cancer patients or at a risk for breast cancer excreted low amounts of both isoflavones and lignans. These results are not surprising since high fiber and vegetarian lignan, precursor-rich diets are generally associated with larger urinary excretion of lignans and with lower breast and colon cancer rates.
It has been postulated that the benefits of high fiber diets containing lignan precursors (and isoflavone phytoestrogens) may, via a production of weakly estrogenic mammalian lignans (and equol) in the intestinal tract, stimulate sex hormone binding globulin (SHBG) in the liver. This action may reduce concentrations of free hormone in the plasma. Since it is well known that oral estrogens (unlike parentally administered) markedly stimulate SHBG—this may present a possible explanation of higher SHBG values found in vegetarians consuming high fiber foods.
In addition to hormonal influence, lignans can provide specific anti-carcinogenic, antiviral, bactericidic and fungistatic benefits, while also yielding antioxidant activity associated with their phenolic structure.
V. Protease Inhibitors
In clinical application, properly cooked or processed soy can yield protease inhibitors, which have demonstrated anti-cancer benefits. Most prominent is their affect against oncogene activation with protective benefits against the harmful effects of radiation and free radicals, which can affect DNA.
VI. Phytosterols
Phytosterols are found exclusively in plant foods and oils, with soy being a significant dietary source. In populations where a high intake of plant food and phytosterols exists -- Japanese, Seventh Day Adventists, vegetarians -- colon cancers have shown to be low.
Chemically, they have a resemblance to cholesterol, and pass primarily unabsorbed through small intestine. Their benefits instead are rendered in the colon where they neutralize bile acids, assist in cholesterol reduction, and provide protection against colon cancer. Other reports indicate diets rich in phytosterols also offer protection against skin cancer.
VII. Phenolic Acids
Phenolic acids are yet other active components of soy. Although research is currently sparse, these substances appear to provide antioxidant properties, and thereby probably inhibit neoplasia.
Gastrointestinal/Hormonal Interactions: Considerations
As illustrated, the influence of various soy components can not be overlooked in terms of hormonal regulation, and overall health benefits. Some of these activities are probably interdependent upon gastrointestinal function.
It has been confirmed that enhanced bile flow is involved in cholesterol clearance. Often overlooked however, is that bile action plays an important role in estrogen clearance. Since about 50% of the estrogen metabolites appear in bile, exclusively in conjugated forms, liver function and the effect of soy protein may be viable considerations for the clinician seeking to enhance bile flow (and perhaps improve liver metabolism) and estrogen clearance.
Secondary to liver/bile function, is the balance of intestinal flora. Intestinal microflora is extensively involved in the metabolism of sex steroid hormones. Only about 7% of estrogen metabolites appear in the feces, the rest being hydrolyzed to the free hormone and reabsorbed in the intestinal tract.
At high fecal microflora concentrations it has been shown that estrone is reduced to estradiol, and 16-alphahydroxyestrone is reduced to estradiol. In vitro incubation of estradiol-3-glucuronide at a low concentration of fecal bacteria results in rapid hydrolysis to free estradiol. Under the same conditions estrone sulfate is converted to estrone, although at slower rate. The composition of resident gastrointestinal microflora therefore plays a critical role in efficient hormonal re-absorption and overall regulation of both estrogens and androgens.
Such research confirms that the gastrointestinal tract functions as a hormone-producing organ. The levels and conversions of multiple estrogens and androgens in the bowel are thus dependent upon healthy internal ecology but also probably closely affected by other variables. These can include diet, stress, liver function, antibiotic and medication use, overall composition of resistant microflora, gut integrity, and probably microflora supporting factors.
Conclusion
The belief that foods contain chemicals that can heal and prevent illness is not new. From ancient use to present day application we are reminded of the therapeutic value of plants ant their unique constituents.
Whether used as a primary dietary protein source or as part of a nutritional supplementation program, the benefits of soy cannot be denied. The use of soybeans and their health protective components provide important advantages for clinical application. Their diverse benefits, including hormonal regulation, cholesterol reduction, immune support, antioxidant and anti-cancer protection remain as some of the key reasons why soy products are being advocated by the nutritional and medical communities alike.
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Joan Friedrich, Ph.D., M.A., CON is an independent consultant to the nutrition and complimentary healthcare communities. Board certified in clinical nutrition as well as several other complimentary modalities, Joan’s books and articles have been extensively published in consumer and professional media. A former director of several NY based nutrition and wellness programs, she has been interviewed on many national broadcasts. In addition to her consulting and lecturing activities, she serves as an advisory board member of Let’s Live and Nutrition Science News. For further information, write: Life-Line, PO Box 482, Bronxville, NY 10708.
