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Limited evidenceWomen's health

Ipriflavone

A synthetic isoflavone derivative for osteoporosis whose largest and best-designed trial was flatly negative — no bone density benefit, no fracture benefit — and which caused lymphocytopenia in a meaningful fraction of women taking it. The positive meta-analyses rest on smaller, older, lower-quality studies.

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What the science says

  • Bone density and fracture prevention Limited evidence

    The definitive test was a 3-year multicenter randomized trial in 474 postmenopausal women taking 600 mg/day ipriflavone plus 500 mg calcium. It found no difference from placebo in lumbar spine bone mineral density and no difference in fracture rate. This was the largest, longest and most rigorous trial ever run on the compound, and it was unambiguously null.

  • Positive pooled analyses Limited evidence

    A 2020 systematic review and meta-analysis did report BMD increases with ipriflavone, but the pooled estimate is driven by smaller, older, largely Japanese and Italian trials with weaker methodology and high heterogeneity. When a large, well-conducted trial contradicts a pool of small ones, the large trial is usually right — this is a textbook case of small-study bias.

  • Lymphocytopenia Moderate evidence

    In the 3-year trial, roughly 13% of women on ipriflavone developed subclinical lymphocytopenia versus a far lower rate on placebo — a statistically significant excess. Counts generally recovered after stopping, but this converts an unproven benefit into a monitored risk, and it is why the compound requires blood count surveillance if used at all.

Dosage & safety

Studied doseThe studied regimen is 600 mg/day, given as 200 mg three times daily with meals, alongside 500 mg/day of calcium. Trials ran 1-3 years. Given the negative outcome of the largest trial and the lymphocyte signal, there is no dose that can currently be recommended.
SafetySubclinical lymphocytopenia occurred significantly more often than with placebo and warrants a complete blood count before starting and periodically thereafter. Gastrointestinal upset is the most common complaint. Ipriflavone inhibits CYP1A2 and CYP2C9, raising levels of theophylline (toxicity has been reported) and tofisopam, and may increase bleeding risk with warfarin. It is metabolized partly to daidzein, so soy-isoflavone cautions apply. Historically a prescription medicine in Japan, Italy and Hungary, it is sold over the counter as a dietary supplement in the United States with no equivalent oversight. Avoid in pregnancy, lactation, and in anyone with renal impairment (clearance is reduced in the elderly). On current evidence it is not a supplement we would recommend.

How to take it

Timing200 mg three times daily with meals, as in the trials, alongside 500 mg/day of calcium.
With food?With meals — this is how it was dosed and it reduces stomach upset.
Worth knowingIf you take it despite the evidence, get a baseline complete blood count and repeat it: subclinical lymphocytopenia was significantly more common than with placebo, and it is silent until someone looks.

Interactions

With medications

  • theophylline

    Ipriflavone inhibits CYP1A2 and raises theophylline levels; toxicity has been reported. do not combine

  • warfarin and other CYP2C9-metabolised drugs

    CYP2C9 inhibition can raise drug levels and bleeding risk. avoid, or only with close INR monitoring on medical advice

  • tofisopam

    Levels rise through the same CYP1A2 inhibition. do not combine

With other supplements

  • soy isoflavones

    Ipriflavone is metabolised partly to daidzein, so it adds to any isoflavone intake and carries the same cautions. do not stack them

Well-established interactions only — this is not a complete list. Always tell your doctor and pharmacist what you take.

Frequently asked questions

Does ipriflavone work for osteoporosis?

No convincing evidence — it is graded limited. The largest trial, 474 postmenopausal women over 3 years on 600 mg/day, found ipriflavone no better than placebo for bone density or fractures.

What are the side effects of ipriflavone?

About 13% of women on ipriflavone developed subclinical lymphocytopenia (low lymphocyte counts) in the 3-year trial, significantly more than on placebo. Anyone taking ipriflavone needs a baseline blood count and periodic repeats.

Is ipriflavone safe with other medications?

Ipriflavone raises theophylline levels, with reported toxicity, and may increase bleeding risk with warfarin. Do not combine ipriflavone with theophylline or tofisopam, and avoid it on warfarin unless your doctor monitors INR closely.

Scientific references

Where to buy

Vital Nutrients, Ipriflavone, 90 Vegan Capsules (300 mg per Capsule)

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