FDA Grants GRAS Designation to Phytosterol Food Supplement

On May 3, the U.S. Food and Drug Administration granted a GRAS (Generally Recognized as Safe) designation to Phytrol, a sitosterol-based food additive manufactured by Forbes Medi-Tech (Vancouver, BC, Canada). The notification paves the way for Forbes to sell Phytrol to food companies as a cholesterol-lowering agent or to market the material as a dietary supplement. Based on favorable results from a double-blind clinical study published last year, the company has already licensed Phytrol to Novartis for use as a functional food ingredient, dietary supplement, and ingredient in over-the-counter cholesterol-lowering products.

Clearing this regulatory hurdle represents a significant milestone for FMT. "The key to successfully marketing Phytrol as a cholesterol-lowering ingredient depends in part on providing consumers with a range of products compatible with individual tastes and a healthy diet," said Forbes Medi-Tech president Tazdin Esmail. "Forbes has developed proprietary methods for incorporating Phytrol into a wide variety of food products."

According to the American Heart Association, nearly 100 million Americans have borderline-to-high cholesterol. Globally, cholesterol-lowering drugs represent an $11 billion market. Merck (Rahway, NJ) controls 40% of the market with its Lipitor ($3.6 billion in sales per year) and Mevacor ($1.1 billion).

Phytrol's "active ingredient" is sitosterol, a steroid found in many plants and oils, including olive and soybean. Sitosterol comprises the same steroid backbone as cholesterol, but its side-chain contains two extra carbons. Most plant steroids contain one (C-28) or two (C-29) carbons more than cholesterol (C-27). Plant-eating insects, who cannot synthesize cholesterol from small carbon sources such as acetate or mevalonate, rely on a dealkylating mechanism to convert 28- and 29-carbon plant steroids to the cholesterol they need to build cell membranes.

In humans, plant steroids act as competitive inhibitors of cholesterol in several biochemical and digestive events. Studies have shown that sitosterol prevents cholesterol adsorption in the gut, inhibits the release of bile salts, and blocks cholesterol esterification. Other research suggests that sitosterol may inhibit acetyl coenzyme-A carboxylase and cholesterol 7 hydroxylase, both key enzymes in cholesterol biosynthesis.

Forbes' sponsored research (see reference) showed that Phytrol's cholesterol-lowering benefits were about equal to that of some cholesterol-lowering drugs. The key finding was a 24.4% reduction in LDL cholesterol in the test group using only Phytrol-spiked margarine compared with an 8.9% reduction for the group on a standardized diet alone. What's striking is that subjects were received the equivalent of only 1.7 grams per day of sitosterol.

Reference

1. Peter JH Jones, Fady Y Ntanios, Mahmoud Raeini-Sarjaz, Catherine A Vanstone. Cholesterol-lowering efficacy of a sitostanol-containing phytosterol mixture with a prudent diet in hyperlipidemic men. American Journal of Clinical Nutrition, 1999:69:1144-50.

For more information: Martin Livingston, Director of Investor Relations, Forbes Medi-Tech, Suite 200 - 750 West Pender St., Vancouver, BC, Canada V6C 2T8. Tel: 604-681-8976. Fax: 604-689-7641.

By Angelo DePalma