Isoflavones

Isoflavones are water-soluble chemicals found in many plants. In this article, we will discuss a group of isoflavones that are phytoestrogens, meaning that they cause effects in the body somewhat similar to those of estrogen. The most investigated phytoestrogen isoflavones, genistein and daidzein, are found in soy products and the herb red clover. One of the ways these isoflavones appear to work is interesting. Although they are less powerful than the body's own estrogen, they latch on to the same places (receptor sites) on cells and don't allow actual estrogen to attach. In this way, when there is not enough estrogen in the body, isoflavones can partially make up for it; but when there is plenty of estrogen, they can partially block its influence. The net effect may be to reduce some of the risks of excess estrogen (breast and uterine cancer) while still providing some of estrogens benefits (preventing osteoporosis). These isoflavones may work in other ways as well, such as by lowering the bodys own level of estrogen. Isoflavones are widely thought to be the active ingredients in soy products. However, the evidence for this theory is inconclusive, and there are some indications otherwise. (See What is the Scientific Evidence for Isoflavones).

Sources

Although isoflavones are not essential nutrients, they may help reduce the incidence of several diseases. Thus isoflavones may be useful for optimum health, even if they are not necessary for life like a classic vitamin. Roasted soybeans have the highest isoflavone content: about 167 mg for a 3.5-ounce serving. Tempeh is next, with 60 mg, followed by soy flour with 44 mg. Processed soy products such as soy protein and soy milk contain about 20 mg per serving. The same isoflavones found in soy are also contained in certain red clover products.

Dosages

The optimum dosage of isoflavones obtained from food is not known. According to one study, 62 mg of isoflavones daily is sufficient to reduce cholesterol. Another study found that 80 mg can reduce menopausal hot flashes, however much remains to be learned.

Uses

Soy products are known to reduce cholesterol; and, soy isoflavones may or may not be their active ingredient.Soy isoflavones may also help prevent some forms of cancer. According to most but not all studies, soy protein or soy isoflavones can reduce menopausal symptoms. Isoflavones from red clover may be helpful too. A small and poorly reported double-blind, placebo controlled study provides weak evidence that red clover isoflavones might be helpful for cyclic mastalgia. There is conflicting evidence regarding whether soy or soy isoflavones may be helpful for preventing osteoporosis. Most but not all studies suggest that use of soy may reduce levels of estrogen slightly. Similarly, most but not all studies found that use of soy lengthens the menstrual cycle by a few days. Both of these effects might lead to reduced risk of breast cancer. Soy failed to prove effective for the hot flashes that often occur in breast cancer survivors.

Scientific Evidence

High Cholesterol In 1995, a review of 38 controlled studies on soy and heart disease concluded that soy is definitely effective at reducing total cholesterol, LDL (bad) cholesterol, and triglycerides. One double-blind study (not part of the review mentioned previously), which involved 66 older women, found improvements in HDL (good) cholesterol as well. The women were divided into three groups. The first group received 40 g of skim milk protein daily. The second group was given the same amount of soy protein, and the third received 40 g of soy protein with extra soy isoflavones. Compared with the skim milk (placebo) group, both soy groups showed significant improvements in both total cholesterol and HDL cholesterol. Although the isoflavones in soy are widely believed to be the active ingredient for lowering cholesterol,34,35,36 several studies have failed to find that isoflavones by themselves are effective. Other, unidentified constituents of soy may be equally or perhaps even more important. For example, it has been hypothesized that various proteins may be the active cholesterol-lowering ingredients of soy. In further support of this possibility, red clover isoflavones, despite their similarity to soy isoflavones, failed to reduce cholesterol levels in a 12-week, double-blind study of 76 women. One possibility is that isoflavones are not the active cholesterol-lowering ingredients in soy. Another possibility is suggested by a study that found that some soy products have an unusual isoflavone profile. Researchers discovered that certain soy products contain high levels of the isoflavone glycitein rather than genistein and daidzein; in most soy products glycitein is a minor constituent. High levels of glycitein could account for some of the negative trials of concentrated soy isoflavones. At present, it is not clear under what circumstances soy might have high glycitein levels, and whether that accounts for the inconsistent results seen in studies. Menopausal Symptoms (Hot Flashes) Although study results are not entirely consistent, isoflavones from soy or red clover appear to be helpful for symptoms of menopause, especially hot flashes, For example, a double-blind, placebo-controlled study involving 104 women found that soy provided significant relief of hot flashes compared to placebo (milk protein). Similarly, a 12-week study of 114 women found improvement in hot flashes and vaginal dryness. Benefits were seen in several other studies as well. Isoflavones from red clover may also be helpful. In a 12 week double-blind, placebo controlled trial of 30 post-menopausal women, use of red clover isoflavones at a dose of 80mg daily significantly reduced hot flash symptoms as compared to placebo. However, some studies (generally of smaller size) have failed to find benefit with soy or concentrated isoflavones. In addition, in a double-blind, placebo-controlled trial of 123 breast cancer survivors, soy failed to reduce hot flashes. The high rate of placebo effect seen in many studies of menopausal symptoms may account for these discrepancies; in such circumstances, small trials can easily fail to identify the benefit of a treatment that is, in fact, effective. It would be helpful to have the results of a large trial (perhaps 300 participant) to fully settle the question, but none has yet been reported. Osteoporosis Evidence regarding whether soy or soy isoflavones are helpful for osteoporosis remains conflicting. In one study that evaluated the benefits of soy isoflavones in osteoporosis, a total of 66 postmenopausal women took either placebo (soy protein with isoflavones removed) or soy protein containing 56 or 90 mg of soy isoflavones daily for 6 months.51 The group that took the higher dosage of isoflavones showed significant gains in spinal bone density. There was little change in the placebo or low-dose isoflavone groups. This study suggests that soy isoflavones may be effective for osteoporosis. Very nearly the same results were also seen in a similar study. This 24-week, double-blind trial of 69 postmenopausal women found that isoflavone-rich soy products can significantly reduce bone loss from the spine. Similar benefits have been seen in some, but not all animal studies and other human trials. Estrogen and most other medications for osteoporosis work by fighting bone breakdown. It has been suggested that soy may also work in the other way, by helping to increase new bone formation.

Safety Issues

Studies in animals have found soy isoflavones essentially nontoxic. While fears have been expressed by some experts that soy isoflavones might interfere with the action of oral contraceptives, one study of 36 women suggests that such concerns are groundless. Because isoflavones work somewhat like estrogen, there are theoretical concerns that they may not be safe for women who have already had breast cancer. Studies in animals have found suggestive evidence that under certain circumstances isoflavones might stimulate breast cancer cells. Furthermore, evidence from two preliminary studies in humans found changes suggesting that soy might slightly increase breast cancer risk. Although other studies in women have found reassuring results, prudence nonetheless suggests that women who have had breast cancer, or are at high risk for it, should consult a physician before taking any isoflavone product. Preliminary studies and reports have raised concerns that intensive use of soy products by pregnant women could exert a hormonal effect that impacts unborn fetuses. Red clover isoflavones might present similar risks. Soy appears to have numerous potential effects involving the thyroid gland. When given to individuals with impaired thyroid function, soy products have been observed to reduce absorption of thyroid medication. In addition, some evidence hints that soy isoflavones may directly inhibit the function of the thyroid gland, though this inhibition may only be significant in individuals who are deficient in iodine. However, to make matters more confusing, studies of healthy humans and animals given soy isoflavones or other soy products have generally found that soy either had no effect on thyroid hormone levels, or actually increased levels. The bottom line: In view of soys complex effects regarding the thyroid, individuals with impaired thyroid function should not take large amounts of soy products except under the supervision of a physician. Additionally, some evidence suggests that the isoflavone genistein 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. 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. While it is too early to conclude that genistein impairs immunity, these findings are a cause for concern. One observational study raised concerns that soy might impair mental function. However, observational studies are less reliable than clinical trials, and other studies hint that soy or soy isoflavones might actually have a beneficial effect on cognition.