Trimethylamine-N-oxide Production and Metabolism

NCT02558673 | Completed

• 1 other identifier: OSP 72118
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Healthy

Keywords

Trimethylamine-N-oxide; Biomarkers; Production; Metabolism; Gut microbiome; Healthy

Outcome Measures

Primary Outcomes (2)

• TMAO biomarkers

  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

  Baseline

Secondary Outcomes (2)

• Flavin monooxygenase 3 (FMO3) 472 G>A

  Baseline

• One-carbon related biomarkers and carnitine

  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)

Study Arms (4)

Egg

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.

Other: TMAO dietary precursors

Beef

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.

Other: TMAO dietary precursors

Fish

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.

Other: TMAO dietary precursors

Fruit

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.

Other: Control (or active comparator)

Interventions

TMAO dietary precursors OTHER

Beef; Egg; Fish

Control (or active comparator) OTHER

Fruit

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)
• Healthy participants who are able to undergo or watch medical procedures

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Cornell University: lead
• American Egg Board: collaborator
• National Cattlemen's Beef Association, a contractor to the Beef Checkoff: collaborator

Study Sites (2)

Gannett Health Services, Cornell University

Ithaca, New York, 14853, United States

Location

Human Metabolic Research Unit, Cornell University

Ithaca, New York, 14853, United States

Location

Related Publications (7)

• Bae S, Ulrich CM, Neuhouser ML, Malysheva O, Bailey LB, Xiao L, Brown EC, Cushing-Haugen KL, Zheng Y, Cheng TY, Miller JW, Green R, Lane DS, Beresford SA, Caudill MA. Plasma choline metabolites and colorectal cancer risk in the Women's Health Initiative Observational Study. Cancer Res. 2014 Dec 15;74(24):7442-52. doi: 10.1158/0008-5472.CAN-14-1835. Epub 2014 Oct 21.

  PMID: 25336191 BACKGROUND

• Bain MA, Fornasini G, Evans AM. Trimethylamine: metabolic, pharmacokinetic and safety aspects. Curr Drug Metab. 2005 Jun;6(3):227-40. doi: 10.2174/1389200054021807.

  PMID: 15975041 BACKGROUND

• Cashman JR, Zhang J, Leushner J, Braun A. Population distribution of human flavin-containing monooxygenase form 3: gene polymorphisms. Drug Metab Dispos. 2001 Dec;29(12):1629-37.

  PMID: 11717182 BACKGROUND

• Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-85. doi: 10.1038/nm.3145. Epub 2013 Apr 7.

  PMID: 23563705 BACKGROUND

• Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922.

  PMID: 21475195 BACKGROUND

• Zhang AQ, Mitchell SC, Smith RL. Dietary precursors of trimethylamine in man: a pilot study. Food Chem Toxicol. 1999 May;37(5):515-20. doi: 10.1016/s0278-6915(99)00028-9.

  PMID: 10456680 BACKGROUND

• Taesuwan S, Cho CE, Malysheva OV, Bender E, King JH, Yan J, Thalacker-Mercer AE, Caudill MA. The metabolic fate of isotopically labeled trimethylamine-N-oxide (TMAO) in humans. J Nutr Biochem. 2017 Jul;45:77-82. doi: 10.1016/j.jnutbio.2017.02.010. Epub 2017 Apr 13.

  PMID: 28433924 DERIVED

Study Officials

• Marie A. Caudill, PhD

  Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2015
• First Posted: September 24, 2015
• Study Start: May 1, 2014
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2016
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

US (2)