Methionine and Cysteine Restriction in Humans

Dietary Methionine and Cysteine Restriction in Overweight Human Subjects

The aim of this study is to examine the effect of methionine and cysteine restriction on energy and macronutrient metabolism in overweight human subjects

Study Overview

• Status: Completed
• Conditions: Overweight
• Intervention / Treatment: Behavioral: Low met/cys diet; Behavioral: Moderate met/cys diet; Behavioral: High met/cys diet

Detailed Description

The sulfur-containing amino acid methionine and its downstream metabolite cysteine has been associated with fat mass in animal studies and human observational studies. Some of the proposed mechanisms include an association with lipogenesis, insulin sensitivity and disrupted energy metabolism.

The overall aim of this project is to evaluate the effects of a diet low in methionine and cysteine on markers of lipids, amino acids, glucose and other biomarkers related to energy metabolism, including transcriptomic and protein expression data from adipose tissue and lymphocytes. Overweight and obese but otherwise healthy volunteers will be randomized to receive a diet either low, moderate or high in methionine and cysteine concentrations for 1 week.

This is a pilot study that may be considered an extension of NCT02647970. In addition to the primary and secondary outcomes we will evaluate the feasibility of the intervention and procedures.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0372
    • University of Oslo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Body mass index of 25-35 kg/m2

Exclusion Criteria:

• High physical activity
• Smoking
• Drugs
• Chronic disease
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low met/cys diet; Dietary intervention	Behavioral: Low met/cys diet; Dietary intervention with low contents of methionine and cysteine
Experimental: Moderate met/cys diet; Dietary intervention	Behavioral: Moderate met/cys diet; Dietary intervention with moderate contents of methionine and cysteine
Active Comparator: High met/cys diet; Dietary intervention	Behavioral: High met/cys diet; Dietary intervention with high contents of methionine and cysteine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma concentrations of amino acids	Measurement of biomarkers of amino acid metabolism, including plasma concentrations of methionine, cysteine and related metabolites	Baseline, Day 1, Day 3 and Day 7 (final visit)
Change in protein expression activity in tissues	Measurement of protein expression and activity related to methionine and cysteine metabolism in adipose tissue and lymphocytes.	Baseline and day 7 (final visit for adipose tissue, Baseline and day 1, 3 and 7 (final visit) for lymphocytes.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma concentrations of fatty acids	Measurement of fatty acid content in plasma	Baseline, Day 1, Day 3 and Day 7 (final visit)
Change in plasma activity indices of steaoryl-CoA desaturase	Calculated based onthe ratio of plasma concentrations of products and precursors	Baseline, Day 1, Day 3 and Day 7 (final visit)
Change in protein expression of steaoryl CoA-desaturase in adipose tissue	Measurement of protein expression of steaoryl CoA-desaturase in adipose tissue	Baseline and Day 7 (final visit)
Change in protein expression of steaoryl CoA-desaturase in lymphocytes	Measurement of protein expression of steaoryl CoA-desaturase in lymphocytes	Baseline, Day 1, Day 3 and Day 7 (final visit)
Change in steaoryl CoA-desaturase activity in adipose tissue	Measurement of enzyme activity of steaoryl CoA-desaturase in adipose tissue	Baseline and Day 7 (final visit)
Diet feasibility	Diet feasibility will be measured by a self-administered questionnaire	Baseline, Day 1, Day 3 and Day 7 (final visit)
Diet compliance	Compliance with the diet will be measured by a self-administered questionnaire	Baseline, Day 1, Day 3 and Day 7 (final visit)
Body composition	Measurement of body composition by bioimpedance and dual X-ray absorptometry	Baseline and day 7 (final visit)

Collaborators and Investigators

• Sponsor: University of Oslo
• Collaborators: The Research Council of Norway; University of Oxford

Publications and helpful links

General Publications

• Olsen T, Ovrebo B, Haj-Yasein N, Lee S, Svendsen K, Hjorth M, Bastani NE, Norheim F, Drevon CA, Refsum H, Vinknes KJ. Effects of dietary methionine and cysteine restriction on plasma biomarkers, serum fibroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study. J Transl Med. 2020 Mar 11;18(1):122. doi: 10.1186/s12967-020-02288-x.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2018
• Primary Completion (Actual): December 11, 2018
• Study Completion (Actual): December 11, 2018

Study Registration Dates

• First Submitted: August 2, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2020
• Last Update Submitted That Met QC Criteria: March 23, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Energy metabolism; Cysteine; Methionine; Sulfur amino acids
• Additional Relevant MeSH Terms: Body Weight; Overweight
• Other Study ID Numbers: 239948-B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No