Herbs & Supplements:
Ipriflavone

Principal Proposed Uses
  • Preventing and Treating Osteoporosis
Other Proposed Uses
  • Reducing the Pain of Osteoporotic Fractures, Bodybuilding

Isoflavones are water-soluble chemicals found in many plants. Ipriflavone is a semisynthetic version of an isoflavone found in soy.

Soy isoflavones have effects in the body somewhat similar to those of estrogen. This should be beneficial, but it is possible that soy could present some of the risks of estrogen as well. In 1969, a research project was initiated to manufacture a type of isoflavone that would possess the bone-stimulating effects of estrogen without any estrogen-like activity elsewhere in the body. Such a product would help prevent osteoporosis but cause no other health risks.

Ipriflavone was the result. After 7 successful years of experiments with animals, human research was started in 1981. Today, ipriflavone is available in over 22 countries and in most drugstores in the United States as a nonprescription dietary supplement. It is an accepted treatment for osteoporosis in Italy, Turkey, and Japan.

According to all but one study, ipriflavone combined with calcium can slow and perhaps slightly reverse bone breakdown. It also seems to help reduce the pain of fractures caused by osteoporosis. However, since it does not appear to have any estrogenic effects anywhere else in the body, it shouldn't increase the risk of breast or uterine cancer. On the other hand, it won't reduce the hot flashes, night sweats, mood changes, or vaginal dryness of menopause, nor prevent heart disease. Ipriflavone is also touted as a bodybuilding aid, but no real evidence supports this use.

Note: A recent, large study found that ipriflavone might reduce white blood cell count in some individuals. See Safety Issues for more information.

Sources

Ipriflavone is not an essential nutrient and is not found to any appreciable extent in food. It must be taken as a supplement.

Therapeutic Dosages

The proper dosage of ipriflavone is 200 mg 3 times daily, or 300 mg twice daily. A calcium supplement providing 1,000 mg of calcium daily should be used as well.

Therapeutic Uses

Ipriflavone appears to be able to slow down and perhaps slightly reverse osteoporosis. It may be helpful for this purpose in ordinary postmenopausal osteoporosis as well as in osteoporosis caused by medications.^1–22 Ipriflavone also seems to ease the pain of fractures caused by osteoporosis.^23,24,25 There is no real evidence that it is helpful for bodybuilding.

What Is the Scientific Evidence for Ipriflavone?

Preventing and Treating Osteoporosis

Numerous double-blind placebo-controlled studies involving a total of over 1,700 participants have examined the effects of ipriflavone on various forms of osteoporosis.^26–37 Overall, it appears that ipriflavone can slow the progression of osteoporosis and perhaps reverse it to some extent. For example, a 2-year double-blind study followed 198 postmenopausal women who showed evidence of bone loss.³⁸ At the end of the study, there was a gain in bone density of 1% in the ipriflavone group and a loss of 0.7% in the placebo group. These numbers may sound small, but they can add up to a lot of bone over time.

Conversely, the largest and longest study of ipriflavone found no benefit.³⁹ In this 3-year trial of 474 postmenopausal women, no differences in the extent of osteoporosis were seen between the ipriflavone and placebo groups. However, for reasons that aren't clear, the researchers in this study gave women only 500 mg of calcium daily. All other major studies of ipriflavone gave participants 1,000 mg of calcium daily. It's possible that ipriflavone requires the higher dose of calcium in order to work properly. (This study also uncovered a significant safety concern. See Safety Issues.)

Ipriflavone, like estrogen, probably works by fighting bone breakdown.^40–43 However, there is some evidence that it may also increase new bone formation, too.^44,45,46

In Combination with Estrogen

Combining ipriflavone with estrogen may enhance anti-osteoporosis benefits.^47,48 However, we do not know for sure whether such combinations increase or reduce the other risks (or benefits) of estrogen. (See Safety Issues for more information.)

Preventing Side Effects of Medications

Ipriflavone may also be helpful for preventing osteoporosis in women who are taking Lupron or corticosteroids, medications that accelerate bone loss.^49,50,51 (However, the combined use of ipriflavone and drugs that suppress the immune system, such as corticosteroids, presents risks. See Safety Issues.)

Reducing Pain of Fractures Caused by Osteoporosis

For reasons that are not at all clear, ipriflavone appears to be able to reduce pain in osteoporosis-related fractures that have already occurred.^52,53,54

Safety Issues

About 3,000 people have used ipriflavone in clinical studies, and, in all but two, no significant adverse effects were seen.^55,56 However, these trials (a 3-year double-blind trial of almost 500 women, as well as a small study) found worrisome evidence that ipriflavone can reduce levels of white blood cells called lymphocytes.^57,58 For this reason, anyone taking ipriflavone long term should have periodic measurements of white blood cell count. In addition, ipriflavone should not be used by anyone with immune deficiencies such as HIV, or by those who take drugs that suppress the immune system, except under physician supervision. There are other potential risks as well. Because ipriflavone is metabolized by the kidneys, individuals with severe kidney disease should have their ipriflavone dosage monitored by a physician.⁵⁹ Individuals with ulcers should also avoid ipriflavone.⁶⁰

Also, although ipriflavone itself does not affect tissues outside of bone, some evidence suggests that if it is combined with estrogen, estrogen's effects on the uterus are increased.^61,62 This might mean that the risk of uterine cancer would be elevated over taking estrogen alone. It should be possible to overcome this risk by taking progesterone along with estrogen, which is standard medical practice in any case. However, this finding does make one wonder whether ipriflavone–estrogen combinations raise the risk of breast cancer too, an estrogen side effect that has no easy solution. At present, there is no available information on this important subject.

Additionally, ipriflavone may interfere with certain drugs by affecting the way they are processed in the liver. For example, it may raise blood levels of the older asthma drug theophylline.^63,64,65 It could also raise levels of caffeine, meaning that if you drink coffee while taking ipriflavone you might stay up longer than you expect! Ipriflavone could also interact with tolbutamide (a drug for diabetes), phenytoin (used for epilepsy), and Coumadin (a blood thinner).⁶⁶ Such interactions are potentially dangerous, especially since phenytoin and Coumadin cause osteoporosis, and some people might be tempted to try taking ipriflavone at the same time.

Interactions You Should Know About

If you are taking

• Theophylline, tolbutamide, Dilantin (phenytoin), Coumadin (warfarin), or any other drug metabolized in the liver: Ipriflavone might change the levels of that drug in your body.
• Estrogen: Ipriflavone might help it strengthen your bones even more. However, it might also increase the risk of uterine cancer.
• Drugs that suppress the immune system, such as corticosteroids or cyclosporine: Do not use ipriflavone except under medical supervision.

Last reviewed March 2002 by Medical Review Board

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