Soy Isoflavones

Overview

Soy Isoflavones, from Glycine max, are phytoestrogens. These weak estrogens are chemically similar in structure to naturally produced estrogen hormones. Isoflavones are found in soy foods both with and without a sugar molecule attached. The two primary isoflavones in soybeans are daidzein and genistein and their respective glucosides, genistein and daidzein. Soy foods typically contain more genistein than daidzein, although this ratio varies among the different soy products. (1)

Isoflavones are studied for a wide spectrum of effects and have been the object of over 1,000 studies. Originally, interest in isoflavones was due to their estrogenic activity (isoflavones can reach relatively high blood levels relative to estradiol (2) in individuals consuming soy foods); however, they are actually very weak estrogens. The soy isoflavones have between 1/1,000 and 1/100,000 the activity of estradiol. (3)

Isoflavones reportedly exhibits effects that are not related to estrogen activity. In vitro studies have reported that genistein inhibits the growth of a wide range of cancer cells including those that are not hormone-dependent. (4) , (5) It has been hypothesized that the explanation for these anticancer effects is the ability of genistein to inhibit the activity of enzymes that control cell growth and regulation. (6)

Dosage Info

Dosage Range

10-300mg daily.

Most Common Dosage

60mg daily.

Dosage Forms

Powders, granules, tablets, capsules, and liquids.

Adult RDI

None estabished

Adult ODA

None established

RDA

Interactions and Depletions

Interactions

Active Forms

Soy isoflavones consist of genistein, daidzein, daidzin, gylcitin, and glycetein.

A synthetic derivative of naturally occurring isoflavones is ipriflavone (7- isopropoxyisoflavone). In animal models, ipriflavone has been shown to prevent bone loss, (7) an effect believed to be related to its ability to enhance calcium absorption. (8)

Absorption

Isoflavones are well absorbed orally.

Toxicities & Precautions

General

There is no known toxicity associated with isoflavones.

Side Effects

One study indicated that ipriflavone, a synthetically derived isoflavone, caused lymphocytopenia in a significant number of women. (9)

Functions in the Body

Mild Estrogenic Activity

Reduce menopausal effects of low estrogen.

Anti-estrogenic Activity

Inhibit cancer-inducing estrogens.

Antioxidant

Studies suggest isoflavones reduce oxidation of LDL.

Enzyme Inhibitor

Enzymes promoting bone resorption are inhibited by isoflavones.

Clinical Applications

Menopause

In women fed 45 grams of soy flour per day, menopause symptoms were reduced by approximately 40 percent. (10) Results of a 5 year randomized, double-blind, placebo-controlled study indicated that soy phytoestrogens administered to postmenopausal healthy women were associated with an increased occurrence of endometrial hyperplasia. (11)

Osteoporosis

Researchers found that after a two year randomized, placebo-controlled trial that daily consumption of two glasses of soymilk containing 76 mg isoflavones prevented lumbar spine bone loss in postmenopausal women suffering from osteoporosis or had at least 3 risk-factors for osteoporosis. (12) Soy isoflavone supplementation to postmenopausal women resulted in significant favorable effects on bone mineral content indicating a possible preventative for osteoporosis. (13)

Hypertension

Though the effect has not been confirmed in humans, soy based diets have reduced blood pressure in hypertensive rats. A randomized, double-blind study involving 40 men and women with mild to moderate hypertension compared the ability of soy milk to lower blood pressure to that of cow’s milk. After 3 months of consumption, individuals in the soy milk group experienced modest, though significant decreases in their blood pressures compared to the those who consumed cow’s milk. (14)

Atherosclerosis And Platelet Aggregation

Genistein reportedly inhibits platelet aggregation and smooth muscle cell proliferation. Smooth muscle cells are one of the primary cell types comprising plaques. (15) , (16) It has been proposed that isoflavones may prevent atherosclerosis including antioxidant effects, antiproliferative and antimigratory effects on smooth muscle cells, effects on thrombus formation, maintenance of normal vascular reactivity, and beneficial effects on plasma lipid concentrations. (17) , (18) , (19) , (20)

Reduce Cancer Risk

Phytoestrogens may have a role in reducing cancer risk. High blood levels of estrogen are a risk factor for breast cancer. By competing with endogenous, estrogen hormones for binding to the estrogen receptor, isoflavones may function as antiestrogens. (21) It has been suggested that the metabolites of genistein may exert anticancer effects. (22) Although only limited data is available, studies suggest that genistein inhibits tumor development (23) and provides anticancer activity. (24) But more studies are warranted before recommending isoflavones for estrogen positive breast cancer because it has also been reported that soy isoflavones stimulate the growth of estrogen-dependent breast cancer cells in vivo in a dose-dependent manner. (25) It has also been reported that high consumption of soy isoflavones may reduce the incidence of prostate cancer in men. (26)

Elevated Cholesterol

Soy protein has been reported to be hypocholesterolemic in individuals with elevated cholesterol. (27) , (28) , (29) Women consuming 60 mg/day of isoflavones for 12 weeks exhibited 3.7% increase in HDL, a 5.5% decrease in the total cholesterol/HDL ratio, and a significant reduction in the oxidation of LDL-cholesterol. (30)

Symptoms and Causes of Deficiency

None documented.

Dietary Sources

Soybeans and soy foods. Raw soybeans contain between 2-4mg of total isoflavones/gram by dry weight. (31) Most soy protein concentrates are low in isoflavones and neither soy sauce or soy oil contain isoflavones. Soy protein concentrates (65 percent soy protein), frequently used in soy burgers and many other soy products, may not contain nutritionally significant amounts of isoflavones. Soy products processed with alcohol to reduce the smell and taste of the soybean have much lower concentrations of isoflavones. Some research suggests that a single serving of soy foods (such as soymilk or tofu) contains enough isoflavones to exert clinical effect. (32)

References

  1. View Abstract: Reinli K, et al. Phytoestrogen Content of Foods–a Compendium of Literature Values. Nutr Cancer. 1996;26(2):123-48.
  2. View Abstract: Xu X, Harris KS, Wang HJ, Murphy PA. Bioavailability of Soybean Isoflavones Depends upon Gut Microflora in Women. J Nutr. 1995;125:2307.
  3. View Abstract: Messina MJ, Persky V, Setchell KDR. Soy Intake and Cancer Risk: A Review of the in Vitro and in Vivo Data. Nutr Cancer. 1994;21:113.
  4. View Abstract: Messina MJ, Persky V, Setchell KDR. Soy Intake and Cancer Risk: A Review of the in Vitro and in Vivo Data. Nutr Cancer. 1994;21:113.
  5. View Abstract: Barnes S, Peterson G. Genistein Inhibition of the Growth of Human Breast Cancer Cells: Independence from Estrogen Receptors and the Multi-drug Resistance Gene. Biochem Biophys Res Comm. 1991;179: 661.
  6. View Abstract: Messina MJ, Persky V, Setchell KDR. Soy Intake and Cancer Risk: A Review of the in Vitro and in Vivo Data. Nutr Cancer. 1994;21:113.
  7. View Abstract: Arjmandi BH, Birnbaum RS, Juma S, et al. The synthetic phytoestrogen, ipriflavone, and estrogen prevent bone loss by different mechanisms. Calcif Tissue Int. Jan2000;66(1):61-5.
  8. View Abstract: Arjmandi BH, Khalil DA, Hollis BW. Ipriflavone, a synthetic phytoestrogen, enhances intestinal calcium transport in vitro. Calcif Tissue Int. Sep2000;67(3):225-9.
  9. View Abstract: Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the Treatment of Postmenopausal Osteoporosis, A Randomized Controlled Trial. JAMA. 2001;285:1482-1488.
  10. View Abstract: Murkies AL, Lombard C, Strauss BJ, et al. Dietary Flour Supplementation Decreases Post-Menopausal Hot Flushes: Effect of Soy and Wheat. Maturitas. 1995;21:189.
  11. View Abstract: Unfer V, Casini ML, Costabile L, Mignosa M, Gerli S, Di Renzo GC. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. Fertil Steril. Jul2004;82(1):145-8.
  12. View Abstract: Lydeking-Olsen E, Beck-Jensen JE, Setchell KD, Holm-Jensen T. Soymilk or progesterone for prevention of bone loss. A 2 year randomized, placebo-controlled trial. Eur J Nutr. Aug2004;43(4):246-57.
  13. View Abstract: Chen YM, Ho SC, Lam SS, Ho SS, Woo JL. Beneficial effect of soy isoflavones on bone mineral content was modified by years since menopause, body weight, and calcium intake: a double-blind, randomized, controlled trial. Menopause. May2004;11(3):246-54.
  14. View Abstract: Rivas M, Garay RP, Escanero JF, Cia P Jr, Cia P, Alda JO. Soy milk lowers blood pressure in men and women with mild to moderate essential hypertension. J Nutr. Jul2002;132(7):1900-2.
  15. View Abstract: Messina MJ, Persky V, Setchell KDR. Soy Intake and Cancer Risk: A Review of the in Vitro and in Vivo Data. Nutr Cancer. 1994;21:113.
  16. View Abstract: Kellie S, Murphy CT, Westwick J. Tyrosine-kinase Activity in Rabbit Platelets Stimulated with Platelet-activating Factor. The Effect of Inhibiting Tyrosine Kinase with Genistein on Platelet-signal-molecule Elevation and Functional Responses. Euro J Biochem. 1993;216:639.
  17. View Abstract: Anthony MS, Clarkson TB, Williams JK. Effects of Soy Isoflavones on Atherosclerosis: Potential Mechanisms. Am J Clin Nutr. Dec1998;68(Suppl6):1390S-93S.
  18. View Abstract: Lichtenstein AH. Soy Protein, Isoflavones and Cardiovascular Disease Risk. J Nutr. Oct1998;128(10): 1589-92.
  19. View Abstract: Petri Nahas E, Nahas Neto J, De Luca L, Traiman P, Pontes A, Dalben I. Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy. Maturitas. Aug2004;48(4):372-80.
  20. View Abstract: Zhuo XG, Melby MK, Watanabe S. Soy Isoflavone Intake Lowers Serum LDL Cholesterol: A Meta-Analysis of 8 Randomized Controlled Trials in Humans. J Nutr. Sep2004;134(9):2395-400.
  21. View Abstract: Tham DM, et al. Clinical Review 97: Potential Health Benefits of Dietary Phytoestrogens: A Review of the Clinical, Epidemiological, and Mechanistic Evidence. J Clin Endocrinol Metab. Jul1998;83(7):2223-35.
  22. View Abstract: Xu X, Harris KS, Wang HJ, Murphy PA. Bioavailability of Soybean Isoflavones Depends upon Gut Microflora in Women. J Nutr. 1995;125:2307.
  23. View Abstract: Barnes LH, Pereira MA, Rasman VL. Use of Azoxymethane-induced Foci of Aberrant Crypts in Rat Colon to Identify Potential Cancer Chemopreventive Agents. Carcinogenesis. 1994;15:1049.
  24. View Abstract: Messina MJ, Persky V, Setchell KDR. Soy Intake and Cancer Risk: A Review of the in Vitro and in Vivo Data. Nutr Cancer. 1994;21:113.
  25. View Abstract: Allred CD, Allred KF, Ju YH, et al. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res. Jul2001;61(13):5045-50.
  26. View Abstract: Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study (United States). Cancer Causes Control. Dec1998;9(6):553-7.
  27. View Abstract: Goodman-Gruen D, Kritz-Silverstein D. Usual dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women. J Nutr. Apr2001;131(4):1202-6.
  28. Sirtori CR, et al. Role of Isoflavones in the Cholesterol Reduction by Soy Proteins in the Clinic. Am J Clin Nutr. Jan1997;65(1):166-67.
  29. View Abstract: Anderson JW, Cook-Newell ME, Johnstone BM. Meta-Analysis of the Effects of Soy Protein Intake on Serum Lipids. NEJM. Aug1995;333:5.
  30. View Abstract: Scheiber MD, Liu JH, Subbiah MT, et al. Dietary inclusion of whole soy foods results in significant reductions in clinical risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women. Menopause. Sep2001;8(5):384-92.
  31. View Abstract: Kaufman PB, et al. A Comparative Survey of Leguminous Plants as Sources of the Isoflavones, Genistein and Daidzein: Implications for Human Nutrition and Health. J Altern Complement Med. 1997;3(1):7-12.
  32. View Abstract: Bingham S, Cassidy A, Setchell KDR. Biological Effects of a Diet of Soy Protein Rich in Isoflavones on the Menstrual Cycle of Premenopausal Women. Am J Clin Nutr. Sep1994;60(3):333.