Ipriflavone (IP), also called ipraflavone, is a massproduced synthetic derivative of genistein (genistin) or daidzein. Genistein and daidzein are unique plant compounds called isoflavones, which are primarily found in soy products. Isoflavones belong to a larger category known as flavonoids, which are natural plant components that have antioxidant, anti-inflammatory, anti-allergy, and anticancer properties.

Although most soy isoflavones are classified as plant estrogens (phytoestrogens), ipriflavone does not have estrogenic activity, and does not activate any estrogen receptors in the body. However, it may prevent or treat bone loss—osteoporosis—associated with menopause (the cessation of menstruation) and aging.

Ipriflavone contains three carbon rings. Its chemical names are:
  • 7-isopropoxyisoflavone
  • 7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one
  • 7-(1-methylethoxy)-3-phenyl-4H-1-benzopyran-4-one
  • 7-isopropoxy-3-phenylchromone

One source notes that ipriflavone is found in foods, but only in trace amounts. In addition to soy products (including some soy sauces), trace amounts are found in alfalfa and other foods. It is also found in propolis, a resin that bees collect from tree buds for use as a hive cement. Ipriflavone is a solid that dissolves only slightly in water.

The liver metabolizes ipriflavone into 7-hydroxy-ipriflavone and 7-(1-carboxy-ethoxy)-isoflavone. IP and its derivatives are bound to albumin, a blood protein, and distributed to tissues throughout the body.

Ipriflavone may be one of the best-studied compounds in the natural health industry. However, the results of these studies are not clear with regard to efficacy in increasing bone density, its primary claim.

Ipriflavone was first isolated at a Hungarian pharmaceutical company in 1969. Since the 1980s, it has been a registered prescription drug for the prevention and treatment of osteoporosis in Japan, Argentina, and Europe.

General use

Like other cells in the human body, bone cells are constantly being replaced. Furthermore, bones serve as a calcium bank because they are a source of calcium used for other functions, such as buffering the blood.

bone defender
bone defender

Osteoporosis is a net loss of bone mass, caused either by excessive bone-resorping (dissolving) or low bone-forming activities. These activities are often related to the increased bone turnover rate that accompanies menopause.

Women have a lifetime risk of 40% for developing osteoporosis. One-half of all women over the age of 50 will develop the disease. One in eight men experience bone fractures as a result of osteoporosis.

Hip fractures caused by osteoporosis are a direct or indirect cause of death in one-quarter of elderly Americans. Bone building and breakdown are influenced by the following:
  • hormones, including estrogen and calcitonin (from the parathyroid gland)\
  • such minerals as magnesium, phosphorus, boron, zinc, silica, and vanadium
  • vitamins, including vitamin D.
  • such other factors as corticosteroid use, sunlight, dietary acidity, physiologic pH, and overall bodily health

Numerous studies have indicated that ipriflavone maintains or increases bone mineral density in osteoporosis, particularly in conjunction with calcium supplementation. Clinical studies have demonstrated that ipriflavone supplementation may:
  • prevent rapid bone loss immediately following menopause
  • increase bone density in postmenopausal women by as much as 3%
  • increase bone mineral density in women with osteoporosis by up to 6%
  • decrease the incidence of bone fractures among post-menopausal women
  • reduce bone pain caused by osteoporosis
  • increase mobility in women with osteoporosis
  • stimulate the synthesis and secretion of calcitonin, a hormone that controls calcium metabolism
  • lower the high cholesterol levels associated with menopausal estrogen deficiency
  • have some activity against cancer

Ipriflavone also slows bone loss in women whose ovaries have been removed, although it does not appear to prevent acute bone loss immediately following ovariectomy.

Further studies in this area have not obtained the same conclusions, except under very specific conditions including younger age and active bone loss. Therefore, the presence of osteoporosis alone does not appear to be sufficient for obtaining good results, even with calcium supplementation.

The mechanisms of ipriflavone activity are not understood. In vitro and animal studies have indicated that:
  • Genistein inhibits the breakdown of bone.
  • Ipriflavone inhibits bone resorption (the breakdown and recycling of bone tissue).
  • Ipriflavone may stimulate bone formation.

In contrast, one large study of postmenopausal women with slight osteoporosis found no significant bone density changes between the group taking calcium supplements alone and those taking calcium plus ipriflavone.

Since ipriflavone does not have estrogenic activity, it may be appropriate for treating bone loss in men, particularly in those with prostate cancer who are receiving therapies that reduce androgen (masculinizing hormone) levels.


Ipriflavone is available over-the-counter (OTC) in many generic and brand name forms (e.g. Ostivone, Natrol, and Bone Support Ipriflavone Blend). It is supplied in capsules, each containg 100, 200, or 300 mg. A typical IP dose for the management of osteoporosis is 200 mg, two to three times daily. Almost all studies consistently used 600 mg daily.

Food items, particularly those containing lipids, increase the small intestine’s absorption of ipriflavone. IP supplements are more effective if combined with calcium and other supplements that help to diminish bone loss during menopause and aging. Ipriflavone sometimes is combined with low-dose estrogen preparations.

Natural isoflavone supplements isolated from soy do not appear to have the same benefits or phytoestrogen neutral qualities as ipriflavone.


Ipriflavone has not been subjected to long-term safety studies. In one study, a consistent precaution resulting from research that spanned as much as three years is that ipriflavone appears to decrease lymphocyte (disease-fighting white-blood-cell) levels in a significant number of postmenopausal women with minor osteoporosis.

Additionally, since ipriflavone is metabolized by the liver, those with liver disease are advised to avoid it unless directed otherwise by a healthcare professional. Other contraindications include pregnancy and breast-feeding, gastric or duodenal ulcers, and kidney disease. Ipriflavone is not recommended for small children.

Side effects

No significant side effects have been observed with ipriflavone, although there are reports of heartburn, nausea, diarrhea, or other mild gastrointestinal disturbances. These side effects may be avoided by taking the supplement with food.

One source noted that the percentage of perceived side effects was actually less among the IP users than in the placebo group. Generally, ipriflavone is considered to be well tolerated, to have no effect on fertility, and to not promote precancerous cellular changes (mutagenicity).

Approximately 13% of women studied had a decrease in white blood cell count, usually within the first six months. However, this group did not become more susceptible to disease or illness.

Their normal white blood cell counts returned within one to two years of discontinuing the IP. There were occasional reports of hypersensitivity reactions and increases in liver function test scores.


Similar to grapefruit juice, IP has an inhibiting effect on a liver detoxification pathway involving an enzyme known as cytochrome P450. This effect increases both the blood levels and the effects of these drugs:
  • theophylline: IP and 7-hydroxy-ipriflavone may inhibit the metabolism and elimination of this asthma drug, leading to elevated—and potentially toxic—blood levels
  • zafirlukast (Accolate), an asthma medication
  • antipsychotic medications
  • caffeine
  • celecoxib (Celebrex), a pain reliever for arthritis
  • cyclobenzaprine (Flexeril), a muscle relaxant
  • nifedipine
  • nonsteroidal anti-inflammatory medications and pain relievers
  • tacrine (Cognex), a medication for Alzheimer’s disease
  • tamoxifen (Nolvadex), for cancer prevention and treatment
  • tolbutamide levels are increased by both ipriflavone and 7-hydroxy isoflavone
  • warfarin (Coumadin), a blood-thinner

The effects of ipriflavone may be additive with the effects of these drugs:
  • bisphosphonates for the treatment of osteoporosis
  • calcitonin
  • estrogen
  • selective estrogen receptor modulators (SERMs)

During the management of osteoporosis, ipriflavone effects may be additive with the effects of the following nutritional supplements: