• Red Clover Isoflavones, Soy 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,
Certain cells in the body have estrogen receptors , special sites that allow estrogen to attach. When estrogen attaches to a cell’s estrogen receptor, estrogenic effects occur in the cell. Isoflavones latch onto estrogen receptors too, but produce weaker estrogenic effects. This leads to an interesting two-part action. When there is not enough estrogen in the body, isoflavones can stimulate cells with estrogen receptors and partly make up for the deficit. However, when there is plenty of estrogen, isoflavones may tend to block real estrogen from attaching to estrogen receptors, thereby reducing the net estrogenic effect. This may reduce some of the risks of excess estrogen (for example, breast and uterine cancer) while still providing some of estrogen's benefits (such as, preventing osteoporosis).
Isoflavones also appear directly to reduce estrogen levels in the body, perhaps by fooling the body into thinking that it has plenty of estrogen.
Isoflavones are widely thought to be the active ingredients in
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 (a cake of fermented soybeans) 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.
When purified isoflavones from red clover or soy are used, the dose generally ranges from about 40 mg to 80 mg daily. This is considerably higher than the average isoflavone intake in Japan, which is about 28 mg daily.
(Post-menopausal Japanese women may consume closer to 50 mg daily.
Soy products are known to improve cholesterol
According to some but not all studies, soy protein or concentrated isoflavones from soy or red clover may slightly reduce
However, isoflavones have failed to prove effective for the hot flashes that often occur in breast cancer survivors.
There is conflicting evidence regarding whether soy or isoflavones may be helpful for preventing
One study tested a purified soy isoflavone product (technically, isoflavone aglycones, as described
A double-blind study performed in China found that use of a soy isoflavone supplement improved blood sugar control in healthy post-menopausal women.
In a small double-blind trial, use of soy isoflavones appeared to reduce some symptoms of
Observational studies also hint that soy might help prevent prostate cancer in men. Men have very low levels of circulating estrogen, so the net effect of increased soy consumption might be to increase estrogen-like activity in the body. Since real estrogen is used as a treatment to suppress prostate cancer, perhaps the mild estrogen-like activity of isoflavones has a similar effect. Isoflavones might also decrease testosterone levels and alter ratios of certain forms of estrogen, both of which which would be expected to provide benefit.
One study failed to find that soy protein with isoflavones improved general quality of life (health status, depression, and life satisfaction) in post-menopausal women.
What Is the Scientific Evidence for Isoflavones?
Numerous studies have found that soy can reduce blood cholesterol levels and improve the ratio of LDL ("bad") versus HDL ("good") cholesterol. 32,33
Although it was once thought that isoflavones are the ingredients in soy responsible for improving cholesterol profile, on balance, current evidence suggests otherwise.
It is also possible that the exact types of isoflavones in a particular product made a difference. One study of red clover isoflavones found evidence that biochanin but not formononetin can reduce LDL cholesterol.
Another study found that soy products may at times have an unusual isoflavone profile, containing high levels of the isoflavone glycitein rather than the more usual genistein and daidzein.
Finally, some evidence hints that soy isoflavones may be only effective for reducing cholesterol when it is converted by intestinal bacteria into a substance called equol.
Although study results are not entirely consistent, the balance of the evidence suggests that isoflavones from soy may be helpful for symptoms of
Improvements in hot flashes, as well as other symptoms, such as vaginal dryness, have been seen in many studies of soy, mixed soy isoflavones, isoflavone aglycones, or genistein alone.
, which also contains a number of isoflavones, has also shown some benefit for menopausal symptoms.
However, several other studies have failed to find benefit with whole soy or concentrated soy isoflavones.
Furthermore, in double-blind, placebo-controlled trials, soy or purified isoflavones failed to reduce hot flashes among survivors of breast cancer.
What can one make of this mixed evidence? The problem here is that placebo treatment has a strong effect on menopausal symptoms. In such circumstances, statistical noise can easily drown out the real benefits of a treatment under study. Estrogen is so powerful for hot flashes and other menopausal symptoms that its benefits are almost always clear in studies; most likely, soy or concentrated isoflavones have a more modest effect, not always seen above the background.
Estrogen has a powerfully protective effect on bone. Study results on whether isoflavones have the same effect have produced inconsistent results.
The best evidence is for genistein taken alone. In a 24-month, double-blind 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.)
However, it is not clear that isoflavones consumed in the diet, even at high concentrations, is beneficial. For example, in a placebo-controlled study involving 237 healthy women in the early stages of menopause, the consumption of isoflavone-enriched foods (providing an average of 110 mg isoflavone aglycones daily) for 1 year had no affect on bone density or metabolism.
Interestingly, one small, but long-term study suggests that
Bone is always subject to two influences: bone building and bone breakdown. Estrogen primarily works by reducing the bone breakdown part of the equation, thereby leading to a net result of increased bone growth. Growing evidence suggests that isoflavones act on both sides of this equation, directly stimulating new bone creation while at the same time slowing bone breakdown.
There is mixed evidence that isoflavones are more effective for osteoporosis in people who have the intestinal bacteria to produce equol.
In a 24-week, double-blind study, 49 women with menstrual migraines (
Studies in animals have found soy isoflavones essentially nontoxic. 65
Still, concerns have been raised about estrogenic and other potential side effects of excessive soy isoflavone intake. Overall, the estrogenic effect of soy isoflavones in women appear to be fairly minimal.
For example, because estrogen can stimulate breast cancer cells, there are theoretical concerns that isoflavones may not be safe for women who have already had breast cancer. While isoflavones in general should have an anti-estrogenic effect by blocking real estrogen, some studies in animals have found evidence that, under certain circumstances, soy isoflavones might stimulate breast cancer cells.
Estrogen also stimulates uterine cells, leading to an increased risk of uterine cancer. Most studies have found that isoflavones do not stimulate uterine cells.
Similarly, preliminary studies and reports have raised concerns that intensive use of soy products or isoflavones by pregnant women could exert a hormonal effect that impacts unborn fetuses.
The drug tamoxifen blocks estrogen and is used to help prevent breast cancer recurrence in women who have had breast cancer. One animal study found that soy isoflavones might remove the benefit of tamoxifen treatment.
One double-blind study of post-menopausal women found the use of red clover isoflavones at a dose of 80 mg daily for 90 days resulted in increased levels of testosterone.
Other concerns relate to soy’s potential effects involving the thyroid gland. When given to individuals with
While fears have been expressed by some experts that soy isoflavones might interfere with the action of oral contraceptives, one study of 36 women found reassuring results.
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.
One observational study raised concerns that soy might impair mental function in adults.
There exists one case report in which soy isoflavone supplements caused migraine headaches in a man who had never experienced migraines before; presumably this was a highly individual reaction, such as an allergy.
Some researchers have raised concern that genistein may influence the ability of blood to clot properly. A placebo-controlled study involving 104 healthy women, however, found no evidence that the isoflavone genistein had any significant adverse effect on blood clotting.
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