Methionine-Restriction Diet (MRD) in Obese Adults With Metabolic Syndrome

The purpose of this study is to determine if limiting dietary methionine (MET), one of the 10 essential amino acids (which make up proteins), causes weight loss and/or improves glucose metabolism.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Methionine deficient diet; Dietary supplement: Methionine sufficient diet

Detailed Description

Methionine deficient diets have been shown to increase metabolic rate, decrease weight and extend lifespan in rodents. A methionine deficient diet has been tested for 17 weeks in humans without adverse events and with an average weight loss of 8 kg. This study will test the ability of a low methionine diet to cause weight loss and improve the metabolic syndrome. The metabolic syndrome is driven by insulin resistance which is associated with abdominal fat, so this study hopes to reduce visceral fat, body weight and improve insulin resistance.

Twenty-four healthy males or females 21 to 60 years of age, inclusive with a stable weight and a waist circumference >40" in men and >35" in women will participate in this study. Subjects will need at least two of the following: 1) HDL cholesterol < 40 mg/dL in men or < 50 mg/dl in women; 2) triglycerides > 150 mg/dL, 3) blood pressure >130/85 mmHg; 4) fasting glucose 110-125 mg/dL. Subjects who have diabetes, a history of heart attack, stroke, have had cancer in the last five years or take chronic medication for a significant illness will be excluded.

Subjects will have a medical history, physical examination, chemistry panel, complete blood count (CBC), electrocardiogram, DEXA, abdominal CT scan to quantitate visceral fat, and blood will be sent to Orentreich for glucose, insulin, C-peptide, lipid profile with particle size, free fatty acids, adiponectin, leptin, high-sensitivity C-reactive protein, and insulin-like growth factor-1. Subjects will also undergo a hyperinsulinemic, euglycemic clamp to quantitate insulin resistance during an 18 hr inpatient stay, and will spend 24 hours in the metabolic chamber to measure metabolic rate. Subjects will then be placed on a diet of Hominex-2, a drink that will give them their protein in an amount based on their body weight, and they will see a dietitian who will give them a list of food they can eat consisting mainly of fruits, vegetables and a small amount of grains. Calories will not be restricted and subjects will receive a choline supplement of 500 mg/d. Subjects will be randomized to receive capsules containing methionine or placebo based on their body weight. The two groups will be on 2mg/kg/d or 23 mg/kg/d of methionine.

Participants will return to PBRC every 2 weeks throughout the 16-week diet period to meet with the dietician, have weight and vital signs recorded, and have fasting blood drawn every 4 weeks to be sent to Orentreich for compliance measures.

The physical exam, multi-slice CT scan, DEXA, inpatient admission for euglycemic hyperinsulinemic clamp, metabolic chamber stay, and the blood testing obtained at screening and baseline will be repeated at the completion of the 16 week diet period.

There are no known risks to the low methionine diet, but some people may have gastrointestinal upsets when they change their diet. The risk of the CT scan is exposure to x-radiation equivalent to a front and side view chest x-ray. The risk of the DEXA is the exposure to x-irradiation equivalent to spending 12 hours in the sunshine. There are no risks to staying in the metabolic chamber. The hyperinsulinemic, euglycemic clamp could cause low blood sugar. This will be avoided by frequent monitoring of blood sugar, and if the low blood sugar were to occur, the test would be stopped and sugar given through the intravenous line. The testing of blood involves the discomfort of a needle going into an arm vein, bruising and rarely fainting or infection. These risks will be minimized by trained technicians using sterile needles.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female between the ages of 21 to 60, inclusive
• Waist greater than 40 inches for men and 35 inches for women
• Weight has been stable for at least 6 months (no more than 5 pounds gained or lost)
• For women of childbearing potential: subject must be willing to use acceptable form of contraception (pill, condom, diaphragm etc.)
• At least 2 of the following:

HDL cholesterol

• Men < 40 mg/dL
• Women < 50 mg/dL Triglycerides ≥150 mg/dL Blood pressure ≥130/≥ 85 mmHg Fasting glucose ≥110-125 mg/dL

Exclusion Criteria:

• Type 1 or Type 2 diabetes
• History of heart attack or stroke
• Pregnant or breastfeeding or planning to become pregnant during the study
• Cancer (other than non-melanoma skin) within the last 5 years
• Significant illness requiring medication
• Inability to read and follow directions in English
• Donated blood in the last 2 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low Methionine 1; Methionine deficient diet	Dietary supplement: Methionine deficient diet; Hominex with a low protein diet; Other Names: Hominex; Methionine
Placebo Comparator: Placebo 2; Placebo comparator methionine complete diet	Dietary supplement: Methionine sufficient diet; Hominex, low protein diet and methionine capsules; Other Names: Hominex; Methionine capsules; Low protein diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Weight loss	Every 2 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Improve glucose metabolism	Baseline and end of study

Collaborators and Investigators

• Sponsor: Pennington Biomedical Research Center
• Collaborators: Orentreich Foundation for the Advancement of Science, Inc.
• Investigators: Principal Investigator: Thomas W Gettys, Ph.D., Pennington Biomedical Research Center

Publications and helpful links

General Publications

• Plaisance EP, Greenway FL, Boudreau A, Hill KL, Johnson WD, Krajcik RA, Perrone CE, Orentreich N, Cefalu WT, Gettys TW. Dietary methionine restriction increases fat oxidation in obese adults with metabolic syndrome. J Clin Endocrinol Metab. 2011 May;96(5):E836-40. doi: 10.1210/jc.2010-2493. Epub 2011 Feb 23.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: March 18, 2008
• First Submitted That Met QC Criteria: March 18, 2008
• First Posted (Estimate): March 21, 2008

Study Record Updates

• Last Update Posted (Estimate): December 18, 2015
• Last Update Submitted That Met QC Criteria: December 17, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Metabolic syndrome; Amino acid; Glucose Metabolism; Methionine; Insulin clamp
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome
• Other Study ID Numbers: PBRC 26009