Soy Isoflavones (genistein, daidzein)

Isoflavones are a class of phytochemicals, which are compounds found only in plants. They are also a type of phytoestrogen, or plant hormone, that resembles human estrogen in chemical structure yet are weaker. By mimicking human estrogen at certain sites in the body, isoflavones provide many health benefits that help you to avoid disease. Isoflavones are found in soybeans, chick peas and other legumes. However, soybeans are unique because they have the highest concentration of these powerful compounds, especially genistein and daidzein.

Isoflavones show tremendous potential to fight disease on several fronts. They have been shown to help prevent the buildup of arterial plaque, which reduces the risk of coronary heart disease and stroke. Isoflavones may help reduce breast cancer by blocking the cancer-causing effects of human estrogen. They may also prevent prostate cancer by hindering cell growth. Isoflavones can fight osteoporosis by stimulating bone formation and inhibiting bone resorption. They may even relieve some menopausal symptoms as well.

Soy isoflavones have antioxidant properties which protect the cardiovascular system from oxidation of LDL (the bad) cholesterol. Oxidized LDL cholesterol accumulates in the arteries as patches of fatty buildup which blocks the flow of blood, resulting in atherosclerosis. Genistein inhibits the growth of cells that form this artery clogging plaque. Arteries damaged by atherosclerosis usually form blood clots. This can lead to a heart attack if the clot goes to the heart, or a stroke if it goes to the brain.

Being a weak form of estrogen, isoflavones can compete at estrogen receptor sites, blocking the stronger version naturally produced by the body from exerting its full effect. Since high blood levels of estrogen are an established risk factor for breast cancer; weaker forms of estrogen may provide protection against this disease. Genistein has been found to hinder breast cancer as well as prostate cancer. Results from a new University of California study show that genistein slowed prostate cancer growth and caused prostate cancer cells to die. It acts against cancer cells in a way similar to many common cancer-treating drugs.

All these findings suggest eating soy foods, natural sources of isoflavones, can protect and enhance your overall health. Isoflavones work together with soy protein in fighting disease. Studies show that isoflavones account for approximately three-fourths of soy’s protection, while its protein is responsible for about one-fourth. The best way to consume isoflavones is in food form, so that you can benefit from all of soy’s nutrients and beneficial compounds. The highest amounts of isoflavones and soy protein are found in tempeh, whole soybeans (like edamame), textured soy protein, soy nuts, tofu and soymilk. Researchers recommend consuming at least one to two servings a day. A serving is equal to 1 ounce of soy nuts; 4 ounces of tempeh, textured soy protein (cooked), or edamame; or 8 ounces of soymilk. Each cup of soy milk contains about 20mg isoflavones (mainly genistein and daidzein).

However, the controversy over the use of soy as a food continues. Here is the conclusion of the Israeli Health Ministry. They recently issued a health advisory strongly recommending that soy foods be eaten only in moderation. They also recommended that soy formula be avoided altogether by infants.

There are hundreds of studies linking soy with such disorders as digestive problems, thyroid dysfunction, ADD and ADHD, dementia, reproductive disorders and cancer.

The Israeli Ministry based its advice on the findings of a panel of nutritionists, oncologists, pediatricians and other specialists who spent over a year looking at the available evidence. They concluded that the phytoestrogens in soy (estrogen-like plant hormones) can be harmful. Their recommendations are in accord with those made by the United Kingdom’s chief medical officer and the British Dietetic Association.

The panel found that:

* The evidence that soy alleviates menopausal symptoms is inconsistent.

* Soy phytoestrogens increase the risk of breast cancer.

* Soy phytoestrogens can also reduce male fertility.

They also noted that while soy has been shown to reduce blood cholesterol, there is no proof that it reduces the risk of heart disease. The panel concluded that the proven risks of soy foods outweigh the possible benefits.

 


Soy Isoflavones (genistein, daidzein) can help with the following

Circulation  

Hypertension

Soy milk consumption (about 2 cups twice per day) reduced systolic and diastolic blood pressure in a double-blind study of 40 men and women with mild to moderate hypertension, when compared to cow’s milk. [J Nutr 2002;132(7): pp.1900-1902] The average systolic blood pressure was reduced 18.4mm Hg, diastolic 15.9mm Hg and mean blood pressure 16.7mm Hg.

The mechanism of action may be independent of isoflavone content, as another study showed no blood pressure lowering benefits with the use of isoflavones alone.



Digestion  

Constipation

Amongst 65 children aged 11 to 72 months with chronic constipation, 68% had a positive response with regard to bowel movements while receiving soy milk.



Hormones  

Hypothyroidism

Soy isoflavones have been found to inhibit the activity of thyroid peroxidase, an enzyme required for thyroid hormone synthesis in cell culture and animal studies [Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action. Biochem Pharmacol. 1997;54(10):pp. 1087-1096. Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect. 2002;110 Suppl 3: pp.349-353.]. However, high intakes of soy isoflavones do not appear to increase the risk of hypothyroidism as long as dietary iodine consumption is adequate. Since the addition of iodine to soy-based formulas in the 1960s, there have been no further reports of hypothyroidism developing in soy formula-fed infants [Pediatrics. 1995;96(1 Pt 1): pp.148-150]. Several clinical trials in premenopausal and postmenopausal women with sufficient iodine intakes have not found high intakes of soy isoflavones to result in clinically significant changes in circulating thyroid hormone levels [J Med Food. 2003;6(4): pp.309-316. Am J Clin Nutr. 2002;75(1):145-153. J Clin Endocrinol Metab. 1999;84(1): pp.192-197. J Clin Endocrinol Metab. 1999;84(10):3479-3484].



Inflammation  

Chronic Inflammation

An article published online on September 23, 2008 in the European Heart Journal reported the finding of researchers at the University of Hong Kong that consuming a soy isoflavone supplement improves vascular endothelial function and reduces C-reactive protein, a marker of inflammation.

In a randomized, double-blinded trial, 102 patients previously diagnosed with ischemic stroke were given an 80 milligram soy isoflavone supplement or a placebo for 12 weeks. Flow-mediated dilatation of the brachial artery, which assesses endothelial function by measuring the ability of the arteries to dilate following a period of impaired circulation, was evaluated on all participants at the beginning of the study and at the end of the treatment period. Fasting blood samples were analyzed for lipids, high-sensitivity C-reactive protein (CRP), markers of oxidative stress, and other factors.



Lab Values  

Elevated Total Cholesterol

A soy protein isolate reduced total and LDL-cholesterol concentrations in a study of 60 patients with high cholesterol levels. [Eur J Clin Nutr 2002;56(4): pp. 352-35]



Musculo-Skeletal  

Gout / Hyperuricemia

Tofu, which is made from soybeans, may be a better choice than meats, when it comes to providing protein in those who have gout.



 

Osteoporosis / Risk

Higher intake of dietary phytoestrogens (isoflavones) was associated with higher lumbar spine and hip bone mineral

densities in a study of 357 postmenopausal southern Chinese women. [J Clin Endocrinol Metab 2001;86(11): pp.5217-5221]

One month of treatment with a soy isoflavone extract reduced the excretion of bone resorption markers, in a placebo-controlled study of 23 healthy perimenopausal women. [J Am Coll Nutr 2002;21(2): pp.97-102]

Another showed that postmenopausal women with the highest level of isoflavone consumption had greater bone mineral density at the spine. [J Women’s Health Gender-Based Med, 2002;11(1): pp.69-78]

If using soy products to reduce osteoporosis risks, consider taking 80mg or more per day of soy isoflavones. One year of supplementation with a soy extract containing 80mg isoflavones in addition to calcium (500mg) and vitamin D3 (125IU) modestly improved hip and trochanter bone mineral density among women with low initial bone mass, compared with placebo OR a lower dose of soy extract containing only 40mg isoflavones with calcium and vitamin D3. This was the conclusion from a well-controlled study of 203 Chinese postmenopausal women. [ J Clin Endocrinol Metab 2003;88(10): pp.4740-7]

Ipriflavone (7-isopropoxyisoflavone) is a synthetic derivative of naturally occuring isoflavones, flavonoid compounds found in soybeans and other plants.

For some time, postmenopausal women in Europe and Japan have taken ipriflavone supplements to maintain the density and strength of their bones and to guard against fractures and other complications associated with the bone-thinning disease known as osteoporosis.

In the United States, ipriflavone supplements have recently become available. Ipriflavone’s bone-strengthening effect is enhanced by taking both vitamin D and calcium along with it.

Because ipriflavone does not have direct estrogenic effects, it may be suitable for use in aging men with bone loss, as well as in women.

However, in 2006, a separate analysis of isoflavones, a component of soy, was also carried out. Dr. Frank Sacks, a professor of nutrition at the Harvard School of Public Health in Boston. According to Dr. Sacks, there are is no evidence that it could reduce symptoms of menopause like ‘hot flashes’ or even osteoporosis.



Organ Health  

Diabetes Type II

Although the mechanism of action is not clear, supplementation with soy protein can reduce insulin resistance, fasting insulin, hemoglobin A1c, total and LDL-cholesterol levels. This was confirmed in a study of 32 postmenopausal women with adult onset diabetes. [Diabetes Care 2002;25(10): pp.1709-1714]



 

Prostatitis

Animal studies suggest that a daily intake of dietary soy protein may play a protective role against the development of prostatitis. [J SterBiochem & Molec Bio, 43: pp.557-564, 1992]



Respiratory  

Asthma

While a higher consumption of whole milk, apples and pears was associated with a reduced risk of asthma and atopy in a study of 1,601 young adults in Australia, a higher intake of soy beverages was associated with an increased risk of asthma and atopy. [Am J Clin Nutr 2003;78(3): pp.414-21]



Risks  

Increased Risk of Prostate Cancer

Soy protein is one of the dietary elements that has been talked about for a long time as having a potentially beneficial effect for preventing prostate cancer. Soybeans are full of chemicals called isoflavones which closely resemble the structure of estrogen-like hormones once widely used to treat prostate cancer.

Laboratory studies are backed up by observations in Asian countries, particularly Japan, where men may develop small prostate tumors but rarely the kind of large, aggressive tumors seen in American men. However, the aggressive form of the cancer becomes more prevalent when Asian immigrants come to the US and are likely to substitute their soy-rich diet with one based mainly on animal protein.

Phytochemicals in soy protect against cancer via several different mechanisms, including interacting with intracellular enzymes, regulating protein synthesis, controlling growth factor actions, inhibiting malignant cell proliferation, inducing differentiation, deterring cancer cell adhesion, and inhibiting angiogenesis.

Since prostate cancer cells usually multiply slowly, the development of prostate cancer can take many years before symptoms appear. During this time period, the benefits of natural therapies like soy consumption are more effective at dealing with the problem while it is still small.

According to a Professor De Sy large quantities of soy products are necessary to be effective against prostate cancer: one must drink 1.5 liters soya milk or 250 grams of soya burger daily. Less than this can be considered when used for prevention purposes.



 

Increased Risk of Bladder Cancer

A higher dietary soy intake was associated with an increased risk of bladder cancer in a study of adults in Singapore

who were followed for three years or longer. [Cancer Epidemiol Biomarkers Prev 2002;11(12): pp.1674-7]



Tumors, Benign  

Colon Polyps

Men who eat one or more servings of soy per week reduce the risk of developing colon polyps by half. [ Am J Epidemiol 1996;44(11): pp.1015-25]



Tumors, Malignant  

Prostate Cancer

Soy extracts provide doses of soy isoflavones such as genistein. Cancer cells use the enzyme protein kinase as a growth factor and genistein is a potent inhibitor of protein kinase activity. The effects of protein kinase inhibitors on human prostate cell growth have been extensively investigated.

Genistein may reduce the metastasic capacity of hormone-dependent cancers. Studies have shown that genistein inhibits proliferation and expression of the invasive capacity of prostatic cancer cells with different invasive potentials. In cell cultures, genistein appears to be cytotoxic and inhibitory of prostate cancer cell proliferation.

Populations that have high soy product consumption are have a low incidence of clinical metastatic prostate cancer, in spite of a sustained high incidence of organ-confined prostate cancer. One study examined genistein’s effect upon cell adhesion as one possible mechanism by which it could be acting as an anti-metastatic agent. Genistein caused cell flattening in a way that prevented metastatic adhesion of prostate cancer cell lines.

Note: Do not take any soy genistein products 10 days prior to, during, or 3 weeks after any form of radiation therapy. Genistein may protect cancer cells against radiation-induced death.

According to a Professor De Sy large quantities of soy products are necessary to be effective against prostate cancer: one must drink 1.5 liters soya milk or 250 grams of soya burger daily.



Uro-Genital  

Menopausal Status / Issues

Although study results are sometimes confusing on the issue of soy extracts and menopause, some studies have shown clear benefit. One such study concluded that a particular soy product “…may be a safe and efficacious therapy for relief of hot flushes in women who refuse or have contraindications for hormone replacement therapy.” [Menopause 2000;7: pp.105-111]

The North American Menopause Society suggests that soy isoflavones can also be a natural alternative to estrogen replacement therapy for relief of mild menopausal symptoms. It may help offset the drop in estrogen and regulate its fluctuations that occur at menopause. Many women have reported a reduction in their hot flashes and night sweats when they regularly consume soy foods, like tempeh or tofu.

Another study found consuming one capsule TID of a soy extract totaling 100mg of soy isoflavones per day effectively alleviated vasomotor symptoms, such as hot flashes, associated with menopause over a 4 month period compared with a placebo. Total cholesterol and low-density lipoproteins were reduced also in the soy isoflavone group compared to placebo. No difference in FSH and LH levels were observed between the placebo and the soy isoflavone group. An increase in estrogen levels was observed only in the soy isoflavone group but this did not result in an increased endometrial thickness. [Obstet Gynecol 2002;99: pp.389-94]

Four months of treatment with a soy isoflavone product reduced the number of hot flashes and other menopausal symptoms in a study of 190 postmenopausal women in Spain. [Phytomedicine 2002;9(2): pp.85-92]

A separate analysis of isoflavones, a component of soy, was also carried out. Dr. Frank Sacks, a professor of nutrition at the Harvard School of Public Health in Boston. According to Dr. Sacks, there are is no evidence that it could reduce symptoms of menopause like ‘hot flashes’ or even osteoporosis.



 

Female Infertility

Women who are trying to conceive may want to heed the following: Avoid eating too much soy. According to a study involving humans, a compound found in soy known as genistein has been found to impair sperm as they swim toward the egg. Even tiny doses of the compound in the female tract could destroy sperm. Genistein can be found in all soy-containing products.

Researchers further explained that avoiding soy around a woman’s more fertile days of the month might actually aid conception.

Based on the findings, a spokeswoman for the Vegetarian Society said that for anyone trying to become pregnant, avoiding soy products for a few days a month is worth a try … even if there is a slim chance it will aid in fertility. [BBC News June 21, 2005]



Key

May do some good
Likely to help
Highly recommended
May have adverse consequences
Reasonably likely to cause problems

Glossary

Phytochemicals

Substances that occur naturally in plants and have been shown in research to possibly prevent or cure disease.

Hormones

Chemical substances secreted by a variety of body organs that are carried by the bloodstream and usually influence cells some distance from the source of production. Hormones signal certain enzymes to perform their functions and, in this way, regulate such body functions as blood sugar levels, insulin levels, the menstrual cycle, and growth. These can be prescription, over-the-counter, synthetic or natural agents. Examples include adrenal hormones such as corticosteroids and aldosterone; glucagon, growth hormone, insulin, testosterone, estrogens, progestins, progesterone, DHEA, melatonin, and thyroid hormones such as thyroxine and calcitonin.

Estrogen

One of the female sex hormones produced by the ovaries.

Stroke

A sudden loss of brain function caused by a blockage or rupture of a blood vessel that supplies the brain, characterized by loss of muscular control, complete or partial loss of sensation or consciousness, dizziness, slurred speech, or other symptoms that vary with the extent and severity of the damage to the brain. The most common manifestation is some degree of paralysis, but small strokes may occur without symptoms. Usually caused by arteriosclerosis, it often results in brain damage.

Cancer

Refers to the various types of malignant neoplasms that contain cells growing out of control and invading adjacent tissues, which may metastasize to distant tissues.

Prostate

The prostate gland in men that surrounds the neck of the bladder and the urethra and produces a secretion that liquefies coagulated semen.

Osteoporosis

A disease in which bone tissue becomes porous and brittle. The disease primarily affects postmenopausal women.

Menopause

The cessation of menstruation (usually not official until 12 months have passed without periods), occurring at the average age of 52. As commonly used, the word denotes the time of a woman's life, usually between the ages of 45 and 54, when periods cease and any symptoms of low estrogen levels persist, including hot flashes, insomnia, anxiety, mood swings, loss of libido and vaginal dryness. When these early menopausal symptoms subside, a woman becomes postmenopausal.

Antioxidant

A chemical compound that slows or prevents oxygen from reacting with other compounds. Some antioxidants have been shown to have cancer-protecting potential because they neutralize free radicals. Examples include vitamins C and E, alpha lipoic acid, beta carotene, the minerals selenium, zinc, and germanium, superoxide dismutase (SOD), coenzyme Q10, catalase, and some amino acids, like cystiene. Other nutrient sources include grape seed extract, curcumin, gingko, green tea, olive leaf, policosanol and pycnogenol.

Cardiovascular

Pertaining to the heart and blood vessels.

Low-Density Lipoprotein

(LDL): Also known as "bad" cholesterol, LDLs are large, dense, protein-fat particles composed of a moderate proportion of protein and a high proportion of cholesterol. Higher levels of LDLs are associated with a greater risk of cardiovascular disease.

Cholesterol

A waxy, fat-like substance manufactured in the liver and found in all tissues, it facilitates the transport and absorption of fatty acids. In foods, only animal products contain cholesterol. An excess of cholesterol in the bloodstream can contribute to the development of atherosclerosis.

Atherosclerosis

Common form of arteriosclerosis associated with the formation of atheromas which are deposits of yellow plaques containing cholesterol, lipids, and lipophages within the intima and inner media of arteries. This results in a narrowing of the arteries, which reduces the blood and oxygen flow to the heart and brain as well as to other parts of the body and can lead to a heart attack, stroke, or loss of function or gangrene of other tissues.

Protein

Compounds composed of hydrogen, oxygen, and nitrogen present in the body and in foods that form complex combinations of amino acids. Protein is essential for life and is used for growth and repair. Foods that supply the body with protein include animal products, grains, legumes, and vegetables. Proteins from animal sources contain the essential amino acids. Proteins are changed to amino acids in the body.

Milligram

(mg): 1/1,000 of a gram by weight.

Thyroid

Thyroid Gland: An organ with many veins. It is at the front of the neck. It is essential to normal body growth in infancy and childhood. It releases thyroid hormones - iodine-containing compounds that increase the rate of metabolism, affect body temperature, regulate protein, fat, and carbohydrate catabolism in all cells. They keep up growth hormone release, skeletal maturation, and heart rate, force, and output. They promote central nervous system growth, stimulate the making of many enzymes, and are necessary for muscle tone and vigor.

Dementia

An acquired progressive impairment of intellectual function. Marked compromise exists in at least three of the following mental activity spheres: memory, language, personality, visuospatial skills, and cognition (i.e., abstraction and calculation).

Oncologist

One who studies cancer.

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