Ipriflavone Fact Sheet

  • Ipriflavone is a synthetic isoflavone.
  • Ipriflavone’s dubious classification as a natural compound invites regulatory agencies to investigate the compound. To date, no studies have convincingly demonstrated that ipriflavone occurs in nature. All published biomedical literature refers to ipriflavone as a synthetic isoflavone.
  • In 1 969 a research project aimed at synthesizing isoflavone derivatives that could exhibit anabolic but not estrogenic activity was started. About 200 new molecules were prepared and screened. Among them, based on the result of several different experimental tests ipriflavone was selected in 1970. In particular, the investigators’ attention focused on the calcium-retaining effect shown by it in in vitro
  • The Japanese registered it as an osteoporosis drug in 1988. Italy, Hungary and a number of other countries soon followed suit.

Estrogenic Effects

  • The estrogenic effects of ipriflavone metabolites on classical estrogen target tissues as well as on bone cell of a different nature need to be studied in detail.
  • Ipriflavone exerts growth promotion and although it increases the uterotropic activity of estrogens, is devoid of estrogenic activity.
  • Its chemical structure resembles that of estrogen and while it augments activity of naturally occurring estrogens it does not have any classical estrogenic effects such as stimulating breast or uterine tissue growth.
  • Ipriflavone metabolites synergize the effects of estradiol — the most potent body estrogen.

Bone Health

  • Osteoprotective effects come from the inhibition of bone resorption — similar to estrogens, which inhibit osteoclast (cells which break bone down) activity or resorption of bone. Results of an animal study done by Japanese researchers suggest that it may inhibit bone breakdown by activating receptors on the surface of osteoclast cells. This prompts calcium to enter the bone-degrading cells, effectively slowing them down. The receptors that accept ipriflavones may exist in human bone but have yet to be identified in human osteoclast cells.
  • Despite the large number of in vivo studies, the mechanisms by which ipriflavone exerts its protective action on the skeleton remain unclear. A direct inhibitory effect of ipriflavone on bone resorption has been demonstrated using rat fetal long bones in culture. In addition, ipriflavone stimulates collagen synthesis in whole-organ cultures of human osteosclerotic auditory samples, suggesting the possibility that it may have a direct effect on osteoblastic cell differentiation.
  • It may activate osteoblasts. When human osteoblasts are exposed to ipriflavone and its metabolites, various cellular processes are enhanced including the manufacture of bone-matrix proteins and bone-mineral deposition (mineralization).
  • Preliminary (1 year) results of double blind placebo controlled studies designed in postmenopausal and senile osteoporosis confirm a reduction in bone turnover rate in patients treated with 600 mg/day of ipriflavone, resulting in a significant bone-sparing effect both at lumbar and radial levels.

Efficacy and Safety

  • It appears that efficacy decreases after the first year of use. Studies so far indicate that ipriflavone’s effect on spinal and forearm bone loss persists only one year after supplementation
  • Long-term effects on bone density and possible side effects have yet to be determined.
  • Ipriflavone may temporarily inhibit certain liver detoxification pathways, resulting in abnormally high blood concentrations of drugs such as theophylline (an asthma drug). People who participated in published ipriflavone trials were screened for such drugs and therefore had no side effects other than minor gastrointestinal complaints. The average postmenopausal female consumer however runs greater risk of ipriflavone­ drug interactions.

References

Almada, Anthony L. “Ipriflavone: The New Bone Builder,” Nutrition Science News. April 1999, Vol3, No. 4:198-200.

Brandi, M. L. “Ipriflavone Influences the Osteoblastic Phenotype in Vitro,” Osteoporosis International. 1993, suppL 1:226-229.

Compston, Juliet E. “Prevention and Management of Osteoporosis,” Drugs. 1997, May 53(5):727-73 5.

Gennari, C. “Ipriflavone: Background,” Calc~fTissue hit. 1997, 6 1:53-54

Reginster, Jean-Yves L. “Ipriflavone: pharmacological properties and usefulness in postmenopausal osteoporosis,” Bone andMineral. 1993, 23:223-232.