The Effect of Dietary Sitosterol on Blood Sugar and Cholesterol

2014-08-27 03:36:08 | BioPortfolio


This study will determine if dietary supplements of sitosterol (a plant cholesterol commonly found in vegetables) can modify blood sugar and cholesterol levels and reduce the stiffness of the blood vessels in people with an abnormal copy of a gene that causes sitosterolemia. People who carry only one copy of the abnormal gene are healthy but have increased blood levels of sitosterol. People with two abnormal copies of the gene have increased levels of sitosterol and have an increased risk of heart attack. This condition is called sitosterolemia. Although extremely rare in the general population, up to 4% of the Amish carry an abnormal copy of this gene.

People of Amish background who are 18 years of age or older and in whom one person carries one copy of the abnormal gene that causes sitosterolemia and the other does not have an abnormal gene may be eligible for this study. Subjects must be of the same sex and within 5 years of age of each other.

During two periods of one month each participants receive pills containing sitosterol and then a special diet and meal supplements to change the levels of sitosterol in the diet. During only one of the two study periods, subjects receive sitosterol supplements in the pills for one month and then for 10 days in the diet. At the end of each study period, subjects come to the NIH Clinical Center for one day for the following tests:

- Measurements of height, weight, blood pressure and heart rate.

- Adipose (fat) tissue biopsy. A small piece of fat from under the skin of the abdomen is removed to examine how sitosterol affects fat tissue and its ability to process sugar and fat.

- Indirect calorimetry. A plastic transparent hood is placed over the subject's head to collect the air that is breathed for about one-half hour to study how the body uses sugar to generate energy.

- Endothelial vascular function. An ultrasound picture of a blood vessel in the forearm is taken and a blood pressure cuff is inflated around the arm to measure the vessel's ability to stretch.

- Intravenous glucose tolerance test: A small plastic tube is placed in a vein in each arm. Then over one minute the subject receives glucose through one of the tubes. Twenty minutes later the subject is given a small amount of insulin through the same tube. Blood samples are drawn through the tube in the other arm at frequent intervals for 3 hours. This test measures how sitosterol affects how the body processes sugar.

- DEXA scan. The subject lies on an x-ray table for 20 minutes during the scan, which measures total body fat.


The relative distribution of the various amounts of lipids in the membranes of the adipocytes plays an important role in lipid metabolism and energy homeostasis. Sitosterolemia, a rare genetic disease, is caused by a defective ABC transporter in the gut and biliary tract, which results in increased absorption and decreased excretion of plant sterols, ultimately leading to accelerated atherosclerosis and premature death.

Very recently, a mutation of the ABCG8 gene, very rare in the general population, has been described in 4 percent of the Old Order Amish, a well-characterized founder population in Lancaster County, Pennsylvania. Preliminary data indicate that otherwise healthy carriers (heterozygotes) of the mutation showed, as compared to controls, reduced body mass index, more large buoyant LDL cholesterol, decreased carotid intima media thickness (IMT), and a trend toward lower insulin and glucose levels, consistent with an improved metabolic syndrome profile. These data suggest that a mild excess in plant sterols could play a role in the modulation of the energy metabolism, and that dietary sitosterol may improve lipid profile and other aspects of the metabolic syndrome in genetically normal subjects.

In order to characterize mechanistically the effects of sitosterol, the most abundant plant sterol in the diet, on the development of the metabolic syndrome, we propose to study in greater detail the carriers of the ABCG8 gene mutation; that will provide the opportunity to analyze new insights into dietary sitosterol and its role in lipid and energy metabolism. We hypothesize that sitosterol in the diet will affect metabolic syndrome indices differentially in carriers of the mutation as compared to non-carriers.

We will perform a nutrigenomics intervention on 15 ABCG8 mutation carriers and sex-matched unaffected persons (age 5 years). They will be treated with high-, low- sitosterol iso-caloric diets. Study subjects will be then evaluated in the NIH Clinical Center for changes in the following parameters: circulating lipids and free fatty acids, glucose disposal, resting energy expenditure and RQ, and endothelial vascular function. The Division of Endocrinology, Diabetes and Nutrition at the University Of Maryland School of Medicine will carry out the genotyping, study volunteer recruitment, cell membrane lipid content analysis, and ex-vivo adipocyte analysis.

We hypothesize that carriers of the ABCG8 gene mutation will further improve metabolic syndrome indices when challenged with a high-sitosterol diet, and will regress toward the non-carrier controls when treated with a low-sitosterol diet. Non-carrier controls will remain unchanged or show modest improvement in metabolic syndrome indices when challenged with a high-sitosterol diet, which will worsen, compared to baseline and carrier sibs, when treated with a low-sitosterol diet.

These clinical data, combined with the in vitro analysis of the effects of sitosterol on cell membranes and adipocyte metabolism will advance knowledge in the field of lipid metabolism on the relation of lipid composition to common disorders such as the metabolic syndrome. Data obtained from this project could then potentially be translated into nutritional and therapeutic interventions in the general population.

Study Design

Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Prevention




High/Low Sitosterol


University of Maryland, Baltimore
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:36:08-0400

Clinical Trials [9 Associated Clinical Trials listed on BioPortfolio]

SCH-58235 (Ezetimibe) to Treat Homozygous Sitosterolemia

This study will test the safety and effectiveness of SCH-58235 (Ezetimibe) in lowering sitosterol, plant sterol and cholesterol blood levels in patients with homozygous sitosterolemia when...

Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia

The purpose of this study is to provide an investigational drug to patients with a specific type of hypercholesterolemia (high cholesterol) or sitosterolemia (unusually high absorption of ...

Sitosterolemia Extension Study

This is an extension study for patients having unusually high absorption of non-cholesterol sterols, resulting in heart-related diseases. This study will evaluate the long term safety and...

Sitosterolemia Extension Study

This is an extension study for patients having unusually high absorption of non-cholesterol sterols, resulting in heart-related diseases. This study will evaluate the long term safety and...

The Multicenter Atorvastatin Plaque Stabilization (MAPS) Study

The impact on cardiovascular events achieved by statin therapy seems to be mostly attributable to the cholesterol-lowering effect with a highly debated contribution of the lipid-independen...

PubMed Articles [11729 Associated PubMed Articles listed on BioPortfolio]

Effect of ezetimibe on low- and high-density lipoprotein subclasses in sitosterolemia.

Sitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL,...

Timely diagnosis of sitosterolemia by next generation sequencing in two children with severe hypercholesterolemia.

Severe hypercholesterolemia associated or not with xanthomas in a child may suggest the diagnosis of homozygous autosomal dominant hypercholesterolemia (ADH), autosomal recessive hypercholesterolemia ...

Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: a brief review of hematological abnormalities of sitosterolemia.

Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PS) usually produce xanthomas and premature co...

Selection of Biodegrading Phytosterol Strains.

The phytosterol-biotransforming strains were selected from Mycobacterium sp., using a high concentration of β-sitosterol. The selection was made by culturing the strains in a medium enriched with 14...

Lipoprotein Apheresis for Sitosterolemia.

Medical and Biotech [MESH] Definitions

A plant genus of the family URTICACEAE. Members contain cryptopleurine, beta-sitosterol, daucosterol and 19 alpha-hydroxyursolic acid.

A plant genus of the family ZINGIBERACEAE. Members contain aculeatin D, beta-sitosterol, and STIGMASTEROL. Some members have been reclassified to ELETTARIA and other ZINGIBERACEAE.

Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.

Ventilatory support system using frequencies from 60-900 cycles/min or more. Three types of systems have been distinguished on the basis of rates, volumes, and the system used. They are high frequency positive-pressure ventilation (HFPPV); HIGH-FREQUENCY JET VENTILATION; (HFJV); and high-frequency oscillation (HFO).

Tools used in dentistry that operate at high rotation speeds.

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