The genistein rush

PillManResearchers rush to discover the medicinal properties of soy-derived substances

A simple search of the medical research literature, using the search-word ‘genistein’, turns up more than 5500 research articles, most of them published in just the past several years. What is the reason for this surge of interest in a substance that, in the 1950s, was believed to be nothing more than a potential anti-fertility agent?

Genistein is an isoflavone extracted from soybeans. It is just one of several isoflavones found in soy and related plants. Daidzein and glycitein are two more, which share some of genistein’s physiological properties as well as having unique properties of their own. In the body, genistein inhibits various enzymes that have wide-ranging actions in many tissues. This means that its physiological effects are diverse and could impact many different ailments. The half-life of genistein supplements in the body is about 8 hours.

Genistein’s structural resemblance to sex hormones, such as estradiol, enables it to alter the body’s response to these hormones. Nonetheless, genistein proved to be a poor fertility blocker. It has, however, attracted the attention of researchers in a variety of fields, especially in cancer and cardiovascular medicine.

Clinical trials, animal studies, cell-culture experiments, and epidemiological studies have provided evidence for the following physiological effects of genistein:

  • reducing symptoms of allergic asthma
  • strengthening bone due to estrogen deficiency, especially in the spine
  • protection of nerve cells from damage caused by hormone shortages and Alzheimer’s proteins
  • breast enlargement
  • inhibition of growth and spread of various cancers – including cancer of the ovaries, colon, prostate, thyroid, skin, and head and neck; non-Hodgkin’s lymphoma, malignant melanoma, certain leukemias and lung cancers, and possibly breast cancer
  • counteracting the effects of the DeltaF508 mutation that causes cystic fibrosis
  • lowering body fat
  • improving insulin responses to blood sugar
  • lowering total cholesterol and LDL levels, increasing HDL levels
  • decreasing symptoms of Raynaud’s disease
  • inhibiting growth of atherosclerotic plaques in blood vessels
  • increasing arterial elasticity, lowering high blood pressure
  • preventing aging effects of UV light on skin
  • enhancing the bioavailability of many hard-to-absorb substances

Let us look at some of these effects in more detail.

Anti-cancer effects

Genistein has displayed antitumor, antimetastatic and antiangiogenic (suppression of blood-vessel growth) properties in tissue culture and in vivo. Several epidemiological studies suggest that soybean consumption may contribute to lower incidence of breast, colon, prostate, thyroid, and head and neck cancers – an effect that is attributed to genistein and other isoflavones. 1, 2, 3, 4, 5, 6

Other cancers that genistein has been reported to inhibit include: non-Hodgkin’s lymphoma, melanoma, lung cancers, and ovarian cancer. 2, 7, 8, 9

Tissue culture experiments suggest that genistein’s cancer-fighting effects occur at dosages that are hard to attain from food alone, unless one eats very large amounts of soy products. Reliable genistein dosing therefore requires the use of concentrated supplements. 4

One study reports that the supplement I3C (indole-3-carbinol) works synergistically with genistein to suppress estrogen-related cancers. 10

Anti-Alzheimer’s effects

Two studies in animals and tissue culture have shown that isoflavones, such as genistein, interfere with the formation of nerve-destroying protein deposits thought to be causes of Alzheimer’s and Parkinson’s diseases. This is not proof that isoflavones can treat these diseases, but it suggests that they might be worth trying. 11, 12

Bone-strengthening effects

The ability of genistein and related soy isoflavones to reduce post-menopausal bone-loss is attested to by many studies. These substances prevent bone loss and promote bone formation, especially in the spine. Among the dosage regimens found to be effective are: 1 mg/day genistein + 0.5 mg/day daidzein + 42 mg/day other isoflavones (biochanin A and formononetin, in this case); 54 mg/day genistein; 57 mg/day isoflavones; 65 mg/day isoflavones; 90 mg/day isoflavones. 13, 14, 15, 16, 17, 18

Short-term dietary soy stimulates breast proliferation in premenopausal, normal breast tissue. 19

Cystic fibrosis

One approach to treating cystic fibrosis is to inhibit a group of intracellular proteins called ‘chaperones’. (This approach applies mainly to a type of cystic fibrosis caused by the ‘DeltaF508’ mutation.) In tissue-culture experiments genistein was able to accomplish exactly that, and has therefore attracted the interest of patients with DeltaF508-related cystic fibrosis. 20

Body fat, insulin, and cholesterol

Genistein appears to increase the rate at which fats are ‘burned’ (metabolized) by the body, and to decrease the rate at which they are deposited in the tissues. 21

In clinical studies of humans and animals, the consumption of genistein and daidzein resulted in loss of body fat, lower fasting insulin concentrations, lower LDL (bad) and higher HDL (good) cholesterol, and improved insulin responses to blood sugar. Cholesterol benefits were seen at dosages of 42 mg/day of genistein plus 27 mg/day of daidzein. 22, 23

Cardiovascular effects

In addition to lowering LDL and raising HDL (mentioned above), genistein prevents the oxidation of LDL – a process thought to contribute to arterial plaques. 24

References

[1] Phase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy isoflavones administered to individuals with cancer. [Abstract]

[2] Isoflavone genistein: photoprotection and clinical implications in dermatology. [Abstract] [Full text] [PDF (823 KB)]

[3] Soy isoflavones and cancer prevention. [Abstract]

[4] Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. [Abstract]

[5] Chemopreventive potential of epigallocatechin gallate and genistein: evidence from epidemiological and laboratory studies. [Abstract]

[6] Emerging evidence on the role of soy in reducing prostate cancer risk. [Abstract]

[7] Genistein sensitizes diffuse large cell lymphoma to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. [Abstract]

[8] Oncogenic pathways implicated in ovarian epithelial cancer. [Abstract]

[9] Pilot study of a specific dietary supplement in tumor-bearing mice and in stage IIIB and IV non-small cell lung cancer patients. [Abstract]

[10] Indole-3-carbinol is a negative regulator of estrogen. [Abstract] [Full text] [PDF (194 KB)]

[11] Attenuation of neurodegeneration-relevant modifications of brain proteins by dietary soy. [Abstract]

[12] Genistein ameliorates beta-amyloid peptide (25-35)-induced hippocampal neuronal apoptosis. [Abstract]

[13] Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. [Abstract] [Full text]

[14] Genistein appears to prevent early postmenopausal bone loss as effectively as hormone replacement therapy. [Abstract]

[15] The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. [Abstract]

[16] Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational, and dietary intervention studies. [Abstract]

[17] The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. [Abstract]

[18] Soy isoflavones: hope or hype? [Abstract]

[19] Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. [Abstract]

[20] Pharmacological approaches to correcting the ion transport defect in cystic fibrosis. [Abstract]

[21] Usual dietary isoflavone intake and body composition in postmenopausal women. [Abstract]

[22] Beneficial role of dietary phytoestrogens in obesity and diabetes. [Abstract]

[23] The effect of isolated soy protein on plasma biomarkers in elderly men with elevated serum prostate specific antigen. [Abstract]

[24] Why are low-density lipoproteins atherogenic? [Abstract]

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