Thursday, October 7, 2010

FDA Recall, Aromatase Inhibitors: What Does It Mean?

BY Dr. Arianna Staruch, ACHS Academic Dean

In case you've seen the FDA post Aromatase Inhibitors in Products Marketed as Dietary Supplements: Recall are are wondering what it all means ...

Aromatase is a cytochrome P450 (CYP) 19 enzyme that is critical in the metabolism of estrogen. In the ovary it is responsible for de novo production of estrogen from cholesterol. In tissues outside the ovary, aromatase converts androgens secreted by the adrenal gland into estrogen.

Aromatase is present in breast tissue and breast fat. Since 60% of premenopausal and 75% of postmenopausal breast cancer patients have estrogen-dependent tumors, this enzyme has been the target of drugs known as aromatase inhibitors. Breast tumors contain an abnormally high level of aromatase that generates a large amount of estrogen. Drug companies began developing inhibitors by modifying androgens, and 4-hydroxyandrostenedione (generic name of formestane) was the first aromatase inhibitor approved for use in breast cancer.

So how does this relate to dietary supplements? Since aromatase is responsible for converting testosterone to estrogen, and increasing testosterone has long been the goal of body builders, adding aromatase inhibitors was thought to be a new way of increasing testosterone and increasing muscle mass. Basically, it is a continuation of the anabolic steroid story made famous by professional athletes.

There are a number of natural aromatse inhibitors found in plants, such as mangosteen and resveratrol (found in grapes). These tend to have very low activity and studies are being done to look at their long-term effects on breast cancer incidence.

So here is the confusion, one of the products recalled by the FDA is called “iForce – Reversitol”, made by I Force Nutrition, a company that caters to the body building community. Resveratrol itself is NOT being recalled, but this product is. The reason is that this product, and others on the recall list, contain the added substance ATD (1,4,6-Androstatriene-3,17-Dione), which is a synthetic aromatase inhibitor. It is basically an unregulated drug, with drug-like side effects. The I-Force product information claims: “An extremely effective AI (Aromatase-inhibitor), ATD eliminates the production of estrogen in the body” and “Similar to Nolvadex, Trans Resveratrol works at the receptor level to block estrogen receptors."

You may know Nolvadex by its generic name, Tamoxifen.

So from a regulatory standpoint, this company added a drug-like substance to their products, compared their product to a drug in their product materials, and failed to show that this substance is Generally Recognized as Safe (GRAS).

The bottom line is, through this recall the FDA is not attempting to restrict access to the dietary supplement resveratrol, but is warning consumers about potential adverse health effects from a product that is not following FDA guidelines.

For more information about estrogen metabolism, aromatase and aromatase inhibitors, see the following papers:

Biochemistry of Aromatase: Significance to Female Reproductive. Physiology1. Kenneth J. Ryan:

Aromatase Inhibitors in the Treatment of Breast Cancer:

History of Aromatase: Saga of an Important Biological Mediator and Therapeutic Target; R. J. Santen, H. Brodie, E. R. Simpson, P. K. Siiteri and A. Brodie:

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