Meta-Analysis of Natural Therapies for Hyperlipidemia
Study Objective: To compare the efficacy and safety of plant sterols and stanols as well as policosanol in the treatment of coronary heart disease, as measured by a reduction in low-density lipoprotein cholesterol (LDL) levels.
Design: Systematic review and meta-analysis of randomized controlled trials.
Patients: A total of 4596 patients from 52 eligible studies.
Measurements and Main Results: We searched MEDLINE, EMBASE, the Web of Science, and the Cochrane Library from January 1967-June 2003 to identify pertinent studies. Reduction of LDL levels was the primary end point; effects on other lipid parameters and withdrawal of study patients due to adverse effects were the secondary end points. Weighted estimates of percent change in LDL were -11.0% for plant sterol and stanol esters 3.4 g/day (range 2-9 g/day [893 patients]) versus -2.3% for placebo (769 patients) in 23 eligible studies, compared with -23.7% for policosanol 12 mg/day (range 5-40 mg/day [1528 patients]) versus -0.11% for placebo (1406 patients) in 29 eligible studies. Cumulative p values were significantly different from placebo for both (p<0.0001). The net LDL reduction in the treatment groups minus that in the placebo groups was greater with policosanol than plant sterols and stanols (-24% versus -10%, p<0.0001). Policosanol also affected total cholesterol, high-density lipoprotein cholesterol (HDL), and triglyceride levels more favorably than plant sterols and stanols. Policosanol caused a clinically significant decrease in the LDL:HDL ratio. Pooled withdrawal rate due to adverse effects and combined relative risk for patients who withdrew were 0% and 0.84, respectively (95% confidence interval [CI] 0.36-1.95, p=0.69), for plant sterols and stanols across 20 studies versus 0.86% and 0.31, respectively (95% CI 0.20-0.48, p<0.0001), for policosanol across 28 studies.
Conclusion: Plant sterols and stanols and policosanol are well tolerated and safe; however, policosanol is more effective than plant sterols and stanols for LDL level reduction and more favorably alters the lipid profile, approaching antilipemic drug efficacy.

Coronary heart disease (CHD) remains the leading cause of death in industrialized nations. Elevated low-density lipoprotein cholesterol (LDL) level is a major risk factor for CHD, hence it is the primary target of lipid-lowering therapy. Due to concerns regarding adverse effects and patient reluctance to comply with chemically derived drug therapies, alternative natural therapies have become increasingly popular over the last decade.

Plant (phyto) sterols are naturally occurring cholesterol derivatives (e.g., sitosterol, campesterol, brassicasterol, stigmasterol) from vegetable oils, nuts, soy, corn, woods, and beans. Hydrogenation of plant sterols produces stanols. Esterification produces sterol and/or stanol esters. The generic term phytosterols often is used to describe both sterols and stanols and their esters. The LDL-lowering efficacy of plant stanols is considered comparable with that of plant sterols. The United States National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III endorses plant sterol and stanol esters 2 g/day as an essential feature of therapeutic lifestyle changes along with diet modifications, weight reduction, intake of viscous fibers, and increased physical activity to reduce risk for CHD.

Another natural product, policosanol, is an antilipemic agent that includes mixtures of aliphatic primary alcohols extracted from sugarcane ( Saccharum officinarum L) wax. Its main components are octacosanol (62.9%), triacontanol (12.6%), and hexacosanol (6.2%). Policosanol is used for reduction of LDL levels in more than 25 countries, mainly in the Caribbean and South America. Clinical studies have demonstrated consistent LDL-lowering activity of policosanol without apparent toxicity concerns.