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Genistein

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Principal Proposed UsesusesOther


Uses

Principal Proposed Uses

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Prevention:
Treatment:
Genistein, a naturally occurring chemical present in soy, has attracted scientific interest for its possible benefits in cancer and heart disease prevention. Genistein is a type of chemical called a phytoestrogen—an estrogen-like substance present in some plants. There are two main types of phytoestrogens: isoflavones and lignans . Soy is the most abundant source of isoflavones, with genistein the most abundant isoflavone in soy. Red clover is also a good source of genistein.
Like other phytoestrogens, genistein can work in two ways: either by increasing or decreasing the effects of estrogen. This happens because genistein binds to special sites on cells called estrogen receptors. Genistein stimulates these receptors, but not as strongly as real estrogen; at the same time, it blocks estrogen itself from attaching. The net result is that when there is a lot of estrogen in the body, such as before menopause, genistein may partly block its effects. Since estrogen appears to increase the risk of various forms of cancer, regular use of genistein by premenopausal women might help reduce this risk. On the other hand, if there is little human estrogen present, such as after menopause, genistein can partly make up for it. This is one rationale for using genistein to treat menopausal symptoms and to prevent osteoporosis.
Genistein might also be helpful for reducing heart disease risk.

Requirements/Sources

Genistein is found in high quantities in soy and in negligible quantities in a few other foods. Most soy foods contain about 1 mg to 2 mg of genistein per gram of protein. 3
For more information on the proper dosage of isoflavones in general, see the full Isoflavone article.

Therapeutic Dosages

The optimum dosage of genistein is unknown. In Asia, population groups who eat soy foods daily containing 20 mg to 80 mg of genistein have lower rates of breast and prostate cancer than do groups in the West with less genistein in their diets. 4 However, we don't know whether genistein (or even soy isoflavones generally) are responsible for this effect.

Therapeutic Uses

Double-blind, placebo-controlled studies have found that genistein may be helpful for preventing heart disease20,21,54 and preventing or treating osteoporosis . 5-10,49 Genistein may additionally improve blood sugar control in people with pre- diabetes . 56 Weaker evidence suggests potential benefits in cancer prevention , 10-12,14-16cancer treatment , 13 and amyotrophic lateral sclerosis (ALS). 22
Isoflavone mixtures containing genistein have undergone considerably more study than genistein alone. Mixed isoflavones have shown promise for most of the conditions just mentioned, as well as menopausal symptoms and cyclic mastalgia .

What Is the Scientific Evidence for Genistein?

Osteoporosis
Estrogen has a powerful protective effect on bone. In women, osteoporosis most often occurs after menopause when the ovaries stop producing estrogen. Animal studies as well as double-blind, placebo-controlled trials in humans suggest that genistein can help restore bone protection. 5-7,49,57
For example, in a 24 month double-blind, placebo-controlled study of 389 postmenopausal women with mild bone loss, use of genistein at a dose of 54 mg daily significantly improved bone density, as compared to placebo. (All participants were additionally given calcium and vitamin D.) 57
In a previous 12-month study, 90 women aged 47 to 57 were given genistein, standard hormone replacement therapy (HRT), or placebo. 49 The results showed that genistein increased bone density to approximately the same extent as HRT. No adverse effects on the uterus or breast were seen.
Interestingly, unlike estrogen, which primarily helps prevent the destruction of bone, evidence suggests that genistein may also assist in creating new bone. 8,9,49
However, in one animal study, while a small dose of genistein helped protect the rats' bones, a larger dose of genistein seemed to have the opposite effect—causing increasing bone destruction. 10 Studies in humans are needed to determine whether genistein is truly effective and to find the optimum dose.
Other studies have evaluated the effects of soy products containing other constituents besides genistein. For more information, see the full Soy and Soy Isoflavones articles.
Menopausal Symptoms (Hot Flashes)
A double-blind study of 247 women suffering from menopausal hot flashes compared the effects of placebo and genistein over a period of one year. 55 Genistein was taken at a dose of 54 mg per day. The results indicated that use of genistein significantly reduced hot flashes as compared to placebo. No adverse effects were seen.
Cancer
Genistein may help reduce risk of various forms of cancer . In one study, newborn female rats treated with genistein had less breast cancer later in life than those treated with placebo. 16 However, other studies suggest that genistein or other isoflavones could promote breast cancer under certain conditions. (See Safety Issues below.)
In the test tube, genistein has been found to suppress the growth of a wide range of cancer cells, including forms of cancer that are not affected by estrogen. 11,12 For example, genistein has been found to inhibit skin cancer when it was applied to the skin of mice or fed to rats. 14,15 Furthermore, in test tube studies, genistein has been found to enhance the effects of chemotherapy drugs . 13
Heart Disease
One double-blind, placebo-controlled study found that use of genistein helped relax the artery wall (the endothelium), an effect that would be expected to help prevent heart disease . 54 In addition, test tube studies suggest that genistein may help keep cholesterol in the blood from depositing in blood vessel walls. 20 Finally, very early test tube research suggests genistein may also inhibit the formation of blood clots, which are a major cause of heart attacks . 21

Safety Issues

Most safety studies that have implications for genistein involved mixed isoflavones from soy or red clover. For more information, see the Safety Issues section of the Isoflavone article.
Regarding genistein alone, one large study reported that genistein caused significant gastrointestinal side effects in almost 20% of participants. 57
Additionally, some evidence suggests that the genistein in particular might impair immunity. One study in mice found that injected genistein has negative effects on the thymus gland (an organ that is important for immunity) and also causes changes in the prevalence of various white blood cells consistent with impaired immunity. 34 Although the genistein was injected rather than administered orally, the blood levels of genistein that these injections produced were not excessively high; they were comparable to (or even lower than) what occurs in children fed soy milk formula. In addition, there are several reports of impaired immune responses in infants fed soy formula. 35-38 While it is too early to conclude that genistein impairs immunity, these findings are a potential cause for concern.

References

1 Messina MJ, Persky V, Setchell KD, et al. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer. 1994;21:113-131.

2 Alhasan SA, Ensley JF, Sarkar FH. Genistein induced molecular changes in a squamous cell carcinoma of the head and neck cell line. Int J Oncol. 2000;16:333-338.

3 Tham DT, Gardner CD, Haskell WL. Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223-2235.

4 Tham DT, Gardner CD, Haskell WL. Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223-2235.

5 Fanti O, Faugere MC, Gang Z, et al. Systematic administration of genistein partially prevents bone loss in ovariectomized rats in a nonestrogen-like mechanism [abstract]. Am J Clin Nutr. 1998;68(suppl):S1517-S1518.

6 Anderson JJ, Ambrose WW, Garner SC. Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model. Proc Soc Exp Biol Med. 1998;217:345-350.

7 Fanti P, Monier-Faugere MC, Geng Z, et al. The phytoestrogen genistein reduces bone loss in short-term ovariectomized rats. Osteoporos Int. 1998;8:274-281.

8 Fanti O, Faugere MC, Gang Z, et al. Systematic administration of genistein partially prevents bone loss in ovariectomized rats in a nonestrogen-like mechanism [abstract]. Am J Clin Nutr. 1998;68(suppl):S1517-S1518.

9 Fanti P, Monier-Faugere MC, Geng Z, et al. The phytoestrogen genistein reduces bone loss in short-term ovariectomized rats. Osteoporos Int. 1998;8:274-281.

10 Anderson JJ, Ambrose WW, Garner SC. Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model. Proc Soc Exp Biol Med. 1998;217:345-350.

11 Messina MJ, Persky V, Setchell KD, et al. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer. 1994;21:113-131.

12 Alhasan SA, Ensley JF, Sarkar FH. Genistein induced molecular changes in a squamous cell carcinoma of the head and neck cell line. Int J Oncol. 2000;16:333-338.

13 Messina MJ, Persky V, Setchell KD, et al. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer. 1994;21:113-131.

14 Wei H, Bowen R, Cai Q, et al. Antioxidant and antipromotional effects of the soybean isoflavone genistein. Proc Soc Exp Biol Med. 1995;208:124-130.

15 Messina MJ, Persky V, Setchell KD, et al. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer. 1994;21:113-131.

16 Tham DT, Gardner CD, Haskell WL. Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223-2235.

17 Tham DT, Gardner CD, Haskell WL. Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223-2235.

18 Crouse JR III, Morgan T, Terry JG, et al. A randomized trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins. Arch Intern Med. 1999;159:2070-2076.

19 Nestel PJ, Yamashita T, Sasahara T, et al. Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler Thromb Vasc Biol. 1997;17:3392-3398.

20 Tham DT, Gardner CD, Haskell WL. Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223-2235.

21 Tham DT, Gardner CD, Haskell WL. Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223-2235.

22 Trieu VN, Uckun FM. Genistein is neuroprotective in murine models of familial amyotrophic lateral sclerosis and stroke. Biochem Biophys Res Commun. 1999;258:685-688.

23 Crowell JA, Levine BS, Page JG, et al. Preclinical safety studies of isoflavones [abstract]. J Nutr. 2000;130(suppl):677S.

24 Petrakis NL, Barnes S, King EB, et al. Stimulatory influence of soy protein isolate on breast secretion in pre- and post-menopausal women. Cancer Epidemiol Biomarkers Prev. 1996;5:785-794.

25 [No authors listed]. Third International Symposium on the role of soy in preventing and treating chronic disease. Washington DC, 1999. J Nutr. 2000;3:S653-S711.

26 Hilakivi-Clarke L, Cho E, Onojafe I, et al. Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring. Oncol Rep. 1999;6:1089-1095.

27 Martini MC, Dancisak BB, Haggans CJ, et al. Effects of soy intake on sex hormone metabolism in premenopausal women. Nutr Cancer. 1999;34:133-139.

28 Divi RL, Chang HC, Doerge DR. Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action. Biochem Pharmacol. 1997;54:1087-1096.

29 Chorazy PA, Himelhoch S, Hopwood NJ, et al. Persistent hypothyroidism in an infant receiving a soy formula: case report and review of the literature. Pediatrics. 1995;96(1 pt 1):148-150.

30 Jabbar MA, Larrea J, Shaw RA. Abnormal thyroid function tests in infants with congenital hypothyroidism: the influence of soy-based formula. J Am Coll Nutr. 1997;16:280-282.

31 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. 2001;61:5045-5050.

32 Ju YH, Allred CD, Allred KF, et al. Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice. J Nutr. 2001;131:2957-2962.

33 Allred CD, Ju YH, Allred KF, et al. Dietary genistin stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with genistein. Carcinogenesis. 2001;22:1667-1673.

34 Yellayi S, Naaz A, Szewczykowski MA, et al. The phytoestrogen genistein induces thymic and immune changes: A human health concern? Proc Natl Acad Sci USA. 2002;99:7616-7621.

35 Zoppi G, Guandalini S. The story of soy formula feeding in infants: a road paved with good intentions. J Pediatr Gastroenterol Nutr. 1999;28:541-543.

36 Zoppi G, Mantovanelli F, Pittschieler K, Delem A, Teuwen DE. Response to RIT 4237 oral rotavirus vaccine in human milk, adapted- and soy-formula fed infants. Acta Paediatr Scand. 1989;78:759-762.

37 Zoppi G. Soy milk feeding and the immune system. Lancet. 1983;2:861.

38 Zoppi G, Zamboni G, Bassani N, Vazzoler G. Gammaglobulin level and soy-protein intake in early infancy. Eur J Pediatr. 1979;131:61-69.

39 Hargreaves DF, Potten CS, Harding C, et al. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab. 1999;84:4017-4024

40 Messina M, Gardner C, Barnes S. Gaining insight into the health effects of soy but a long way still to go: commentary on the fourth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease. J Nutr. 2002;132:547S-551S.

41 Doerge DR, Sheehan DM. Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect. 2002;110(suppl 3):349-353.

42 Chang HC, Doerge DR. Dietary genistein inactivates rat thyroid peroxidase in vivo without an apparent hypothyroid effect. Toxicol Appl Pharmacol. 2000;168:244-252.

43 Bell DS, Ovalle F. Use of soy protein supplement and resultant need for increased dose of levothyroxine. Endocr Pract. 2001;7:193-194.

44 Duncan AM, Merz BE, Xu X, et al. Soy isoflavones exert modest hormonal effects in premenopausal women. J Clin Endocrinol Metab. 1999;84:192-197.

45 Almir F, Staack R, Jeffrey E, et al. An extract of soy flour influences serum cholesterol and thyroid hormones in rats and hamsters. J Nutr. 1996;126:3046-3053.

46 Potter SM, Pertile J, Berber-Jimenez MD. Soy protein concentrate and isolated soy protein similarly lower blood serum cholesterol but differently affect thyroid hormones in hamsters. J Nutr. 1996;126:2007-2011.

47 Forsythe WA 3rd. Soy protein, thyroid regulation and cholesterol metabolism. J Nutr. 1995;125(suppl 3):619S-623S.

48 Persky VW, et al. Effect of soy protein on endogenous hormones in postmenopausal women. Am J Clin Nutr. 2002;75:145-153.

49 Morabito N, Crisafulli A, Vergara C, et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. J Bone Miner Res. 2002;17:1904-1912.

50 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. 2001;61:5045-5050.

51 Ju YH, Allred CD, Allred KF, et al. Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice. J Nutr. 2001;131:2957-2962.

52 Allred CD, Ju YH, Allred KF, et al. Dietary genistin stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with genistein. Carcinogenesis. 2001;22:1667-1673.

53 White LR, Petrovitch H, Ross GW, et al. Brain aging and midlife tofu consumption. J Am Coll Nutr. 2000;19:242-255.

54 Squadrito F, Altavilla D, Crisafulli A, et al. Effect of genistein on endothelial function in postmenopausal women: a randomized, double-blind, controlled study. Am J Med. 2003;114:470-476.

55 D'Anna R, Cannata ML, Atteritano M, et al. Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebo-controlled study. Menopause. 2007 Jan 23. [Epub ahead of print]

56 Atteritano M, Marini H, Minutoli L, et al. Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: a 2-years randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2007 May 22. [Epub ahead of print]

57 Marini H, Minutoli L, Polito F, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women. Ann Intern Med. 2007;146:839-847.

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