TSI Refutes JAMA Article On Ipriflavone
TSI Health Sciences, Inc. (TSI) released statements today asserting the report1 published in the March 21, 2001 Journal of the American Medical Association (JAMA) concerning the dietary supplement ipriflavone draws conclusions that contradict the preponderance of data from clinical studies conducted over the past 15 years.
Eight double-blind placebo controlled studies previously conducted on ipriflavone showed a statistically significant bone-sparing effect over the placebo among a total population size of more than 850 post-menopausal women. These studies provided the rationale for what was originally named the Ipriflavone Multicenter European Fracture Study (IMEFS); with a stated hypothesis that 21% of the placebo group would experience a vertebral fracture within 3 years and that ipriflavone would lead to a 50% reduction in fractures2.
Due to a high, and unexplained, dropout rate in the study (40%), it lacked the necessary statistical power to maintain the original goal of a fracture study. Thus the name IMEFS was dropped and the study’s focus shifted.
Two noticeable abnormalities occurred in the study reported in JAMA which strongly suggest that the results could be “population dependent? First, the placebo group’s bone densities remained stable. And secondly, only 4.5% of the placebo group experienced new vertebral fractures, compared to the going-in hypothesis of 21% that was based on similar populations1.
The report states ipriflavone does not prevent bone loss, yet the data presented (figure 2) contradicts this statement. Bone Mass Densities (BMD’s) for the ipriflavone population were stable over the duration of the study1.
Ipriflavone safety concerns are cited as “the reduced lymphocyte counts were statistically significant, from 33% (1900) to 27% (1400).? These are within normally acceptable ranges5. While these reductions may be statistically significant, the fact that they were subclinical (ie. clinically asymptomatic) means that their clinical relevance is unknown. Drug induced lymphopenia is fairly common, but it does not necessarily mean that it is clinically significant6.
Summary data from over 60 ipriflavone studies performed in Italy, Japan, and Hungary indicate out-of-range lymphocyte counts less than 3%, sharply contrasting a value of 13% reported in the study. Italy’s Chiesi Farmaceutici (a study underwriter) reported the incidence of all complaints for ipriflavone (14.5%) less than that of the placebo (16.1%) in their post-marketing studies3 and pharmaceutical manufacturer Takeda of Japan, the first to introduce ipriflavone, indicated only four cases (0.06%) of leukocytopenia in their 1988 to 1994 post marketing report4.
According to TSI president, Larry Kolb, “This type of study and its publication is expected because ipriflavone is being marketed in the U.S. as a dietary supplement. We are disappointed that a prestigious journal such as JAMA would publish a study with so many unanswered questions and misleading conclusions. Of course it is no surprise that the mainstream press is quick to embrace it and continue to malign dietary supplements?
“The fact remains that the overwhelming body of published evidence, including research studies, pre- and post-marketing reports, and experience in the US market and abroad, supports the use of ipriflavone as a dietary supplement,?continued Kolb. “TSI reaffirms its confidence in its Ostivone® ipriflavone.?
TSI introduced Ostivone® ipriflavone as a raw material for use in dietary supplements in 1997 after going through appropriate pre-market notification to FDA. Approximately 70 million?00 mg doses of Ostivone® ipriflavone products have been sold in the U.S. without known incident since its introduction. Information available to the Company indicates that there have been no Adverse Event Reports (AER’s) filed with FDA’s MedWatch or any other reporting agency.
TSI is a leading researcher, producer, and marketer of nutraceutical ingredients to the dietary supplement, pharmaceutical, and food and beverage industries. Its products include botanical, marine, and natural product extracts and synthesized compounds.
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1 Ipriflavone in the Treatment of Postmenopausal Osteoporosis, A Randomized Control Trial; JAMA, March 21, 2001; Vol.285, No 11.
2 Design for an Ipriflavone Multicenter European Fracture Study; Regnister, et.al., Tissue International 1997
3 Efficacy of Ipriflavone in Established Osteoporosis and Long-Term Safety; Agnusdei and Bufalino; Calcified Tissue International (1997) 61:523-527
4 Takeda Corp., Osteoporosis Therapeutic Agent / Ipriflavone; Adverse Effects and Changes in Clinical Examination; October, 1998.
5 The Merck Manual of Diagnosis and Therapy, 17th Edition, Chapter 127, Section 11, pa 854;.
6 Drug-Induced Lymphopenia: Focus on CD+4 and CD+8 Cells; Drug Safety, August 1999, Vol. 21, no. 2, pp 91-100(10)
NOTE TO EDITORS: Please contact the company for accurate information regarding Ostivone?ipriflavone. Clinical studies are available upon request from the company, as are third-party authored books, such as Better Bones, Better Body by Susan E. Brown, Ph.D.
TSI Health Sciences
Toll Free: 877-549-9123
