Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial.
BACKGROUND
Herbal extracts from Commiphora mukul (guggul) have been widely used in Asia as cholesterol-lowering agents, and their popularity is increasing in the United States. Recently, guggulsterones, the purported bioactive compounds of guggul, have been shown to be potent antagonists of 2 nuclear hormone receptors involved in cholesterol metabolism, establishing a plausible mechanism of action for the hypolipidemic effects of these extracts. However, there are currently no published safety or efficacy data on the use of guggul extracts in Western populations.


OBJECTIVE
To study the short-term safety and efficacy of 2 doses of a standardized guggul extract (guggulipid, containing 2.5% guggulsterones) in healthy adults with hyperlipidemia eating a typical Western diet.


METHODS
Double-blind, randomized, placebo-controlled trial using a parallel design, conducted March 2000-August 2001.


METHODS
A total of 103 ambulatory, community-dwelling, healthy adults with hypercholesterolemia in the Philadelphia, Pa, metropolitan area.


METHODS
Oral, 3 times daily doses of standard-dose guggulipid (1000 mg), high-dose guggulipid (2000 mg), or matching placebo.


METHODS
Percentage change in levels of directly measured low-density lipoprotein cholesterol (LDL-C) after 8 weeks of therapy. Secondary outcome measures included levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, and directly measured very low-density lipoprotein cholesterol (VLDL-C), as well as adverse events reports and laboratory safety measures including electrolyte levels and hepatic and renal function.


RESULTS
Compared with participants randomized to placebo (n = 36), in whom levels of LDL-C decreased by 5%, both standard-dose guggulipid (n = 33) and high-dose guggulipid (n = 34) raised levels of LDL-C by 4% (P =.01 vs placebo) and 5% (P =.006 vs placebo), respectively, at 8 weeks, for a net positive change of 9% to 10%. There were no significant changes in levels of total cholesterol, HDL-C, triglycerides, or VLDL-C in response to treatment with guggulipid in the intention-to-treat analysis. While guggulipid was generally well tolerated, 6 participants treated with guggulipid developed a hypersensitivity rash compared with none in the placebo group.


CONCLUSIONS
Despite plausible mechanisms of action, guggulipid did not appear to improve levels of serum cholesterol over the short term in this population of adults with hypercholesterolemia, and might in fact raise levels of LDL-C. Guggulipid also appeared to cause a dermatologic hypersensitivity reaction in some patients.
Szapary
Philippe O
PO
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA. szapary@mail.med.upenn.edu
Wolfe
Megan L
ML
Bloedon
LeAnne T
LT
Cucchiara
Andrew J
AJ
DerMarderosian
Ara H
AH
Cirigliano
Michael D
MD
Rader
Daniel J
DJ
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D029744:Commiphora; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000627:therapeutic use*; D053149:Plant Gums; D011282:Pregnenediones / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D008074:Lipoproteins; D010936:Plant Extracts; D053149:Plant Gums; D011282:Pregnenediones; C018562:guggulu extract; C023617:pregna-4,17-diene-3,16-dione