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.
Note: A recent, large study found that ipriflavone might reduce white blood cell count in some individuals. See Safety Issues for more information.
Ipriflavone is not an essential nutrient and is not found in food. It must be taken as a supplement.
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 taken as well.
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
Ipriflavone has also been proposed as a bodybuilding aid, but there is no meaningful evidence that it is helpful for this purpose.
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.
However, 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. How can this failure be accounted for in view of all the successful trials that came before? Perhaps because 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.
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
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.
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 potential risks. See Safety Issues.)
Finally, 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
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 for the long-term should have periodic measurements taken 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. 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.
If you are taking:
References
1. Gennari C, Adami S, Agnusdei D, et al. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Calcif Tissue Int . 1997;61(suppl 1):S19-S22.
2. Valente M, Bufalino L, Castiglione GN, et al. Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass. Calcif Tissue Int . 1994;54:377-380.
3. Kovacs AB. Efficacy of ipriflavone in the prevention and treatment of postmenopausal osteoporosis. Agents Actions . 1994;41:86-87.
4. Adami S, Bufalino L, Cervetti R, et al. Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years. Osteoporos Int . 1997;7:119-125.
5. Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int . 1997;61(suppl 1):S23-S27.
6. Agnusdei D, Crepaldi G, Isaia G, et al. A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int . 1997;61:142-147.
7. Benvenuti S, Petilli M, Frediani U, et al. Binding and bioeffects of ipriflavone on a human preosteoclastic cell line. Biochem Biophys Res Commun. 1994;201:1084-1089.
8. Bonucci E, Silvestrini G, Ballanti P, et al. Cytological and ultrastructural investigation on osteoblastic and preosteoclastic cells grown in vitro in the presence of ipriflavone: preliminary results. Bone Miner . 1992;19(suppl 1):S15-S25.
9. Brandi ML. Ipriflavone influences the osteoblastic phenotype in vitro. Osteoporos Int . 1993;3(suppl 1):226-229.
10. Cheng SL, Zhang SF, Nelson TL, et al. Stimulation of human osteoblast differentiation and function by ipriflavone and its metabolites. Calcif Tissue Int . 1994;55:356-362.
11. Cecchettin M, Bellometti S, Cremonesi G, et al. Metabolic and bone effects after administration of ipriflavone and salmon calcitonin in postmenopausal osteoporosis. Biomed Pharmacother . 1995;49:465-468.
12. Civitelli R. In vitro and in vivo effects of ipriflavone on bone formation and bone biomechanics. Calcif Tissue Int . 1997;61(suppl 1):S12-S14.
13. Agnusdei D, Camporeale A, Zacchei F, et al. Effects of ipriflavone on bone mass and bone remodeling in patients with established postmenopausal osteoporosis. Curr Ther Res . 1992;51:82-91.
14. Melis GB, Paoletti AM, Bartolini R, et al. Ipriflavone and low doses of estrogens in the prevention of bone mineral loss in climacterium. Bone Miner . 1992;19(suppl 1):S49-S56.
15. Nozaki M, Hashimoto K, Inoue Y, et al. Treatment of bone loss in oophorectomized women with a combination of ipriflavone and conjugated equine estrogen. Int J Gynaecol Obstet . 1998;62:69-75.
16. Gambacciani M, Cappagli B, Piaggesi M, et al. Ipriflavone prevents the loss of bone mass in pharmacological menopause induced by GnRH-agonists. Calcif Tissue Int . 1997;61(suppl 1):S15-S18.
17. Yamazaki I, Shino A, Shimizu Y, et al. Effect of ipriflavone on glucocorticoid-induced osteoporosis in rats. Life Sci . 1986;38:951-958.
18. Gambacciani M, Spinetti A, Piaggesi L, et al. Ipriflavone prevents the bone mass reduction in premenopausal women treated with gonadotropin hormone-releasing hormone agonists. Bone Miner. 1994;26:19-26.
19. Agnusdei D, Zacchei F, Bigazzi S, et al. Metabolic and clinical effects of ipriflavone in established post-menopausal osteoporosis. Drugs Exp Clin Res. 1989;15:97-104.
20. Passeri M, Biondi M, Costi D, et al. Effects of 2-year therapy with ipriflavone in elderly women with established osteoporosis. Ital J Miner Electrolyte Metab. 1995;9:137-144.
21. Agnusdei D, Adami S, Cervetti R, et al. Effects of ipriflavone on bone mass and calcium metabolism in postmenopausal osteoporosis. Bone Miner. 1992;19 (suppl 1):S43-S48.
22. Melis GB, Paoletti AM, Cagnacci A. Ipriflavone prevents bone loss in postmenopausal women. Menopause. 1996;3:27-32.
23. Maugeri D, Panebianco P, Russo MS, et al. Ipriflavone-treatment of senile osteoporosis: results of a multicenter, double-blind clinical trial of 2 years. Arch Gerontol Geriatr . 1994;19:253-263.
24. Moscarini M, Patacchiola F, Spacca G, et al. New perspectives in the treatment of postmenopausal osteoporosis: ipriflavone. Gynecol Endocrinol . 1994;8:203-207.
25. Scali G, Mansanti P, Zurlo A, et al. Analgesic effect of ipriflavone versus sCalcitonin in the treatment of osteoporotic vertebral pain. Curr Ther Res . 1991;49:1004-1010.
26. Gennari C, Adami S, Agnusdei D, et al. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Calcif Tissue Int . 1997;61(suppl 1):S19-S22.
27. Valente M, Bufalino L, Castiglione GN, et al. Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass. Calcif Tissue Int . 1994;54:377-380.
28. Kovacs AB. Efficacy of ipriflavone in the prevention and treatment of postmenopausal osteoporosis. Agents Actions . 1994;41:86-87.
29. Adami S, Bufalino L, Cervetti R, et al. Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years. Osteoporos Int . 1997;7:119-125.
30. Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int . 1997;61(suppl 1):S23-S27.
31. Agnusdei D, Zacchei F, Bigazzi S, et al. Metabolic and clinical effects of ipriflavone in established post-menopausal osteoporosis. Drugs Exp Clin Res. 1989;15:97-104.
32. Agnusdei D, Crepaldi G, Isaia G, et al. A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int. 1997;61:142-147.
33. Maugeri D, Panebianco P, Russo MS, et al. Ipriflavone-treatment of senile osteoporosis: results of a multicenter, double-blind clinical trial of 2 years. Arch Gerontol Geriatr. 1994;19:253-263.
34. Passeri M, Biondi M, Costi D, et al. Effects of 2-year therapy with ipriflavone in elderly women with established osteoporosis. Ital J Mineral Electrolyte Metab. 1995;9:137-144.
35. Agnusdei D, Adami S, Cervetti R, et al. Effects of ipriflavone on bone mass and calcium metabolism in postmenopausal osteoporosis. Bone Miner. 1992;19 (suppl 1):S43-S48.
36. Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA. 2001;285:1482-1488.
37. Melis GB, Paoletti AM, Cagnacci A. Ipriflavone prevents bone loss in postmenopausal women. Menopause. 1996;3:27-32.
38. Agnusdei D, Crepaldi G, Isaia G, et al. A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int . 1997;61:142-147.
39. Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA. 2001;285:1482-1488.
40. Agnusdei D, Crepaldi G, Isaia G, et al. A double blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int . 1997;61:142-147.
41. Benvenuti S, Petilli M, Frediani U, et al. Binding and bioeffects of ipriflavone on a human preosteoclastic cell line. Biochem Biophys Res Commun . 1994;201:1084-1089.
42. Bonucci E, Silvestrini G, Ballanti P, et al. Cytological and ultrastructural investigation on osteoblastic and preosteoclastic cells grown in vitro in the presence of ipriflavone: preliminary results. Bone Miner . 1992;19(suppl 1):S15-S25.
43. Brandi ML. Ipriflavone influences the osteoblastic phenotype in vitro. Osteoporos Int . 1993;3(suppl 1):226-229.
44. Cheng SL, Zhang SF, Nelson TL, et al. Stimulation of human osteoblast differentiation and function by ipriflavone and its metabolites. Calcif Tissue Int . 1994;55:356-362.
45. Cecchettin M, Bellometti S, Cremonesi G, et al. Metabolic and bone effects after administration of ipriflavone and salmon calcitonin in postmenopausal osteoporosis. Biomed Pharmacother . 1995;49:465-468.
46. Civitelli R. In vitro and in vivo effects of ipriflavone on bone formation and bone biomechanics. Calcif Tissue Int . 1997;61(suppl 1):S12-S14.
47. Melis GB, Paoletti AM, Bartolini R, et al. Ipriflavone and low doses of estrogens in the prevention of bone mineral loss in climacterium. Bone Miner . 1992;19(suppl 1):S49-S56.
48. Nozaki M, Hashimoto K, Inoue Y, et al. Treatment of bone loss in oophorectomized women with a combination of ipriflavone and conjugated equine estrogen. Int J Gynaecol Obstet . 1998;62:69-75.
49. Gambacciani M, Cappagli B, Piaggesi M, et al. Ipriflavone prevents the loss of bone mass in pharmacological menopause induced by GnRH-agonists. Calcif Tissue Int . 1997;61(suppl 1):S15-S18.
50. Yamazaki I, Shino A, Shimizu Y, et al. Effect of ipriflavone on glucocorticoid-induced osteoporosis in rats. Life Sci . 1986;38:951-958.
51. Gambacciani M, Spinetti A, Piaggesi L, et al. Ipriflavone prevents the bone mass reduction in premenopausal women treated with gonadotropin hormone-releasing hormone agonists. Bone Miner. 1994;26:19-26.
52. Maugeri D, Panebianco P, Russo MS, et al. Ipriflavone-treatment of senile osteoporosis: results of a multicenter, double-blind clinical trial of 2 years. Arch Gerontol Geriatr . 1994;19:253-263.
53. Moscarini M, Patacchiola F, Spacca G, et al. New perspectives in the treatment of postmenopausal osteoporosis: ipriflavone. Gynecol Endocrinol . 1994;8:203-207.
54. Scali G, Mansanti P, Zurlo A, et al. Analgesic effect of ipriflavone versus sCalcitonin in the treatment of osteoporotic vertebral pain. Curr Ther Res . 1991;49:1004-1010.
55. Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int . 1997;61(suppl 1):S23-S27.
56. Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA. 2001;285:1482-1488.
57. Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int. 1997;61 (suppl 1):S23-S27.
58. Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA. 2001;285:1482-1488.
59. Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int . 1997;61(suppl 1):S23-S27.
60. Matsuoka M, Yoshida Y, Hayakawa K, et al. Gastrojejunal fistula caused by gastric ulcer. J Gastroenterol. 1998;33:267-271.
61. Petilli M, Fiorelli G, Benvenuti U, et al. Interactions between ipriflavone and the estrogen receptor. Calcif Tissue Int . 1995;56:160-165.
62. Cecchini MG, Fleisch H, Muhibauer RC. Ipriflavone inhibits bone resorption in intact and ovariectomized rats. Calcif Tissue Int . 1997;61(suppl 1):S9-S11.
63. Takahashi J, Kawakatsu K, Wakayama T, et al. Elevation of serum theophylline levels by ipriflavone in a patient with chronic obstructive pulmonary disease [letter]. Eur J Clin Pharmacol . 1992;43:207-208.
64. Monostory K, Vereczkey L. Interaction of theophylline and ipriflavone at the cytochrome P450 level. Eur J Drug Metab Pharmacokinet . 1995;20:43-47.
65. Monostory K, Vereczkey L. The effect of ipriflavone and its main metabolites on theophylline biotransformation. Eur J Drug Metab Pharmacokinet . 1996;21:61-66.
66. Monostory K, Vereczkey L, Levai F, et al. Ipriflavone as an inhibitor of human cytochrome P450 enzymes. Br J Pharmacol . 1998;123:605-610.
Last reviewed April 2009 by EBSCO CAM Review Board
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