Overview

This trial has been completed.

Condition healthy
Treatments tmao dietary precursors, control (or active comparator)
Sponsor Cornell University
Collaborator American Egg Board
Start date May 2014
End date July 2014
Trial size 40 participants
Trial identifier NCT02558673, OSP 72118

Summary

The purpose of this study was to understand the production of trimethylamine-N-oxide (TMAO) and its metabolites from dietary precursors found in fish, eggs and beef. In addition, this study traced the fate of supplemental TMAO that has been labeled with deuterium to determine how TMAO is being used in the body.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model crossover assignment
Masking open label
Primary purpose basic science
Arm
(Experimental)
Study meals were administered in commonly consumed serving sizes (3 hard-boiled eggs) and provided comparable amounts of TMAO dietary precursors. Each meal was served with one cup of water, administered in a single day and separated by a 1-week washout period.
tmao dietary precursors
(Experimental)
Study meals were administered in commonly consumed serving sizes (6 oz beef [Philly-Gourmet Beef Patties]) and provided comparable amounts of TMAO dietary precursors. Each meal was served with one cup of water, administered in a single day and separated by a 1-week washout period.
tmao dietary precursors
(Experimental)
Study meals were administered in commonly consumed serving sizes (6 oz fish [cod fillet]) and provided comparable amounts of TMAO dietary precursors. Each meal was served with one cup of water, administered in a single day and separated by a 1-week washout period.
tmao dietary precursors
(Active Comparator)
Study meals were administered in commonly consumed serving sizes (2 single-serve packages of Mott's natural applesauce) and provided comparable amounts of control (or active comparator). Each meal was served with one cup of water, administered in a single day and separated by a 1-week washout period. For the fruit control, 50 mg deuterium-labeled methyl-d9-TMAO (d9-TMAO; Cambridge Isotopes) was added to one cup of water for oral consumption to enable the tracing of the metabolic fate of TMAO, and to assess its bioavailability and clearance.
control (or active comparator)

Primary Outcomes

Measure
TMAO biomarkers
time frame: Assess change from baseline; randomized, controlled, cross-over design with 4 study sessions with 1-week wash-out between visits. Participants were followed for 6 h (egg, beef and fish), and for 6-24 h (fruit + d9-TMAO)
Gut microbiome profile
time frame: Baseline

Secondary Outcomes

Measure
Flavin monooxygenase 3 (FMO3) 472 G>A
time frame: Baseline
One-carbon related biomarkers and carnitine
time frame: Assess change from baseline; randomized, controlled, cross-over design with 4 study sessions with 1-week wash-out between visits. Participants were followed for 6 h (egg, beef and fish), and for 6-24 h (fruit + d9-TMAO)

Eligibility Criteria

Male participants from 21 years up to 50 years old.

Inclusion Criteria (main study): - Healthy men of age 21-50 y - BMI of 20-29.9 kg/m2 who are willing to comply with the study protocol (consumption of study meals and sample collections) Inclusion Criteria (sub-study involving muscle biopsy): - Healthy participants who are able to undergo or watch medical procedures Exclusion Criteria (main study): - Men over 50 y of age - BMI ≥ 30 kg/m2 - Women, vegetarians, smokers, individuals with gastrointestinal diseases or complaints, chronic illnesses or other metabolic diseases (including trimethylaminuria), abnormal laboratory values, and those taking nutritional supplements, antibiotics or probiotics within 2 months of recruitment. Exclusion Criteria (sub-study involving muscle biopsy): - Men with history of a negative or allergic reaction to local anesthetics - Tendency toward easy bleeding or bruising, on medications that may increase the chance of bleeding or bruising (e.g., Aspirin, Coumadin, Anti-inflammatories, Plavix) - Currently on any immunosuppressive medications (e.g., glucocorticoid steroids, chemotherapy), with disease pathologies that would impair the healing process (e.g., diabetes, cancer, keloids, hereditary healing disorders, jaundice, alcoholism, HIV/AIDS)

Additional Information

Official title Impact of Diet and Gut Microbiota on Trimethylamine-N-oxide Production and Fate in Humans
Principal investigator Marie A. Caudill, PhD
Description Trimethylamine-N-oxide (TMAO) is a carbon-containing organic compound formed from dietary precursors including TMAO (high in fish), choline (high in eggs) and carnitine (high in beef). However, TMAO production is highly variable (Zhang AQ et al., 1999), appears to be influenced by genetics (Cashman JR et al., 2001) and gut microbiome (Wang Z et al., 2011; Koeth RA et al., 2013), and is linked to heart disease in cardiac patients (Wang Z et al., 2011) and colorectal cancer among post-menopausal women (Bae S et al., 2015). At present, very little is known about the metabolic fate of TMAO and how it is used within the human body (Bain MA et al., 2005). This study sought to (i) quantify the effects of eggs, beef and fish on TMAO biomarkers in plasma, muscle, urine and stool; (ii) examine the metabolic fate of supplemental TMAO labeled isotopically with deuterium; and (iii) determine whether TMAO production is a function of the gut microbiome. To accomplish these objectives, a randomized, controlled cross-over study was conducted in healthy male participants (n=40). The study incorporated four arms comprised of study meals representing animal sources of TMAO (egg, beef and fish) along with a fruit control. The study meals were (i) 3 whole hard-boiled eggs; (ii) 6 oz beef (Philly-Gourmet Beef Patties); (iii) 6 oz fish (cod fillet); and (iv) 2 single-serve packages of Mott's natural applesauce. Each meal was served with one cup of water, administered in a single day and separated by a 1-week washout period. For the fruit control, 50 mg deuterium-labeled methyl-d9-TMAO (d9-TMAO; Cambridge Isotopes) was added to one cup of water for oral consumption to enable the tracing of the metabolic fate of TMAO, and to assess its bioavailability and clearance. Baseline blood sample was obtained by a phlebotomist using a standard venipuncture procedure, and participants collected their baseline urine sample. They also turned in self-collected baseline 24 h urine and stool samples. Following the consumption of the study meal, serial blood samples were collected at 15, 30 min and 1, 2, 4 and 6 h, while urine samples were collected throughout the 6 h study period. At 4.5 h, participants were provided a fixed fruit snack (i.e., applesauce) and water. On the day that participants consumed the d9-TMAO tracer, participants collected their urine throughout the next 24 h and their stool at the next bowel movement. In addition, a subset of this group (n=6) were invited to undergo a muscle biopsy procedure 6 h after the fruit + d9-TMAO tracer consumption.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Cornell University.