Abstract 206: Randomized Double Blind Clinical Trial on the Effect of Oral Alpha-cyclodextrin on Serum Lipids

Abstract

Despite numerous therapeutic advances, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in developed countries. Statins, currently the most effective therapeutic agents for reducing CVD risk, only reduce cardiovascular events by approximately 30%. One possible complementary approach for lowering LDL-C involves the use of oral agents that complex or associate with dietary fats, preventing their intestinal absorption. Bile acid sequestrants are among the oldest lipid-altering drugs and have been known for decades to improve lipid levels and also improve glucose control. Alpha-cyclodextrin (a-CD), a cyclical polymer containing 6 glucose sub-units, is found in many foods, drinks and is sold as an over the counter food supplement. a-CD has a hydrophobic central cavity that binds lipids; one gram of a-CD binds as much as 9 grams of dietary fat and animal studies as well as clinical trials showed that it reduces dietary lipid absorption. This is the first study that evaluated the effect of a-CD in healthy subjects and was designed as a single center, double-blinded, cross-over, placebo controlled clinical pilot study. We screened 103 subjects, males and females, and obtained 75 completed studies (42% male, 58% female, mean age 34 ±12 y.o., BMI 25±4 kg/m2). Eligible subjects were randomized into two arms and received placebo or a-CD (6 grams P.O. a day; two 1 gram tablets per meal) for 12-14 weeks with a one week of wash out period between arms. Several biochemistry and lipid parameters were analyzed and statistics were performed using paired t-test. a-CD was well tolerated and no serious adverse events related to a-CD were observed. Minor GI symptoms were the most common complaint but occurred in less than 7% of subjects on a-CD (vs 3% in placebo). No significant differences were detected on serum lipid and other lipid values but fasting serum glucose (-13% a-CD vs placebo), insulin (-7% a-CD vs placebo), HbA1C (-6% a-CD vs placebo) were decreased. Further positive alterations were present in individuals with higher glucose levels. In conclusion, in healthy subjects, a dose of 6 grams a day of a-CD was able to improve plasma glucose related indexes, in the population studied, but had no significant effect in lipid or lipoprotein plasma levels.