Clinical trial NCT06758856: Effect of Betaine and Choline on Metabolic Health
Official title: ABC (Additional Betaine and Choline) Study: Effect of Betaine and Choline Intake on Biomarkers of Metabolic Health in Humans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obesity and Obesity-related Medical Conditions
Keywords: Betaine
Choline
Overweight
Obesity
Metabolism
Lead sponsor: University of Guelph
Sponsor class: OTHER
First posted: 2025-01-06
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this research is to determine whether extra betaine and choline influence metabolic health in adults with overweight and obesity.

Detailed description: Betaine (N,N,N-trimethylglycine or also glycine betaine) is a derivative of choline that functions as an organic osmolyte and participates in one-carbon metabolism as a methyl donor. Betaine is naturally found in beets, wheat and spinach and sold as a food supplement without prescription. Choline is recognized as an essential nutrient that is found in various foods including eggs, nuts and beef, with the major form of choline in food found as phosphatidylcholine. In addition to being oxidized to the methyl donor betaine, choline is a precursor of several compounds involved in neurotransmitter synthesis, lipid metabolism and transport as well as the structural integrity and signaling of cell membranes. Previous studies have reported alterations in one-carbon metabolites in response to a single meal containing different forms of choline, with interindividual variability dependent on genetics and gut microbiota composition. This study will extend to longer-term impact of different forms of choline (betaine as oxidized choline and choline provided from food) with a focus on overweight and obesity, which comprise a predominant portion of the population in North America. The objective of this study is to determine the effect of betaine supplementation with or without food-form choline (eggs) on metabolic health in adults with overweight and obesity. A randomized crossover study design will be employed, which men and women of age 18-70 years with BMI 25-35 kg/m2 will participate in a 14-week study consisting of three 4-week dietary periods: 1) daily consumption of 3 grams of betaine supplement with no eggs; 2) daily consumption of 3 grams of betaine supplement with 3 whole eggs; and 3) daily consumption of 3 grams of cellulose supplement with no eggs, in a random order, each dietary period separated by a 1-week washout break. Blood, urine and fecal samples as well as anthropometric measurements will be collected at baseline, then at weeks 4, 9 and 14. The collected biological samples will be used to measure glucose and lipid markers, one-carbon metabolites and profiling of gut microbiota and genotype to determine interindividual differences in metabolism.

Eligibility criteria: Inclusion Criteria:

* Male or female participant of any race or ethnicity between 18-70 years of age (inclusive) at the time of informed consent
* BMI between 25-35 kg/m2
* Non-smoker
* Willing to consume 3 eggs per day for one dietary period of 4 weeks
* Willing to avoid eggs during the rest of the study including washout period breaks except for eggs that are provided
* Willing to fast before the baseline and dietary period lab visits
* Willing to provide a 24-hr prior day food record at the dietary period lab visits
* Willing to provide or collect biological specimen samples at the baseline and dietary period lab visits
* Willing to follow the study protocol including maintaining usual lifestyle during the entire study

Exclusion Criteria:

* Male or female \< 18 years or \> 70 years of age at the time of consent
* BMI \< 25 kg/m2; or BMI \> 35 kg/m2
* Pregnant or planning to become pregnant during the course of the study; currently breastfeeding or postpartum \< 6 months
* Use of hormone therapy including birth control pills
* Follows a vegan diet
* Current smoker (any form of nicotine, e-cigarettes, etc)
* Use of recreational drugs (may affect metabolic pathway for choline)
* Presence of chronic illnesses, e.g., heart disease, diabetes, cancer, celiac disease, inflammatory bowel disease (Crohn's disease and ulcerative colitis), gastrointestinal liver or kidney diseases or alcoholism
* Diagnosis of trimethylaminuria (genetic disorder affecting choline use in body)
* Use of antibiotics in the last 2 months
* Use of prebiotics, probiotics or dietary fiber (i.e., Metamucil) supplements in the last 2 months
* Have allergies to eggs or any anaphylactic food allergies
* Have a schedule or lifestyle patterns incompatible with the study protocol

Primary outcomes:
measure: Lipid panel
timeFrame: Weeks 0, 4, 9 and 14
measure: Glucose concentrations
timeFrame: Weeks 0, 4, 9 and 14
measure: Insulin concentrations
timeFrame: Weeks 0, 4, 9 and 14
measure: Concentrations of glucose metabolism panel
timeFrame: Weeks 0, 4, 9 and 14
measure: Body mass
timeFrame: Weeks 0, 4, 9 and 14
measure: One-carbon metabolism panel
timeFrame: Weeks 0, 4, 9 and 14
Secondary outcomes:
measure: Gene expression
timeFrame: Weeks 0, 4, 9 and 14
measure: Inflammatory response in immune cells
timeFrame: Weeks 0, 4, 9 and 14
measure: Composition of the gut microbiota
timeFrame: Weeks 0, 4, 9 and 14
measure: Characterization of single nucleotide polymoprhisms
timeFrame: Week 0
measure: Liver health panel
timeFrame: Weeks 0, 4, 9 and 14
measure: Blood cell counts
timeFrame: Weeks 0, 4, 9 and 14
measure: Blood pressure
timeFrame: Weeks 0, 4, 9 and 14
measure: Dietary intake
timeFrame: Weeks 0, 4, 9 and 14
Other outcomes:
Locations:
city: Guelph
country: Canada
facility: Human Nutraceutical Research Unit
state: Ontario
Study officials:
References:
citation: Zeisel SH, da Costa KA. Choline: an essential nutrient for public health. Nutr Rev. 2009 Nov;67(11):615-23. doi: 10.1111/j.1753-4887.2009.00246.x.
citation: Wallace TC, Blusztajn JK, Caudill MA, Klatt KC, Natker E, Zeisel SH, Zelman KM. Choline: The Underconsumed and Underappreciated Essential Nutrient. Nutr Today. 2018 Nov-Dec;53(6):240-253. doi: 10.1097/NT.0000000000000302. Epub 2018 Nov 13.
citation: Lever M, Slow S. The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clin Biochem. 2010 Jun;43(9):732-44. doi: 10.1016/j.clinbiochem.2010.03.009. Epub 2010 Mar 25.
citation: Craig SA. Betaine in human nutrition. Am J Clin Nutr. 2004 Sep;80(3):539-49. doi: 10.1093/ajcn/80.3.539.
citation: Cho CE, Taesuwan S, Malysheva OV, Bender E, Tulchinsky NF, Yan J, Sutter JL, Caudill MA. Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial. Mol Nutr Food Res. 2017 Jan;61(1). doi: 10.1002/mnfr.201600324. Epub 2016 Aug 3.
citation: Cho CE, Aardema NDJ, Bunnell ML, Larson DP, Aguilar SS, Bergeson JR, Malysheva OV, Caudill MA, Lefevre M. Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men. Nutrients. 2020 Jul 25;12(8):2220. doi: 10.3390/nu12082220.