Clinical trial NCT06687122: Egg Intake, Metabolic Outcomes and Choline Levels
Official title: Additional Daily Intake of Eggs for Improving Metabolic Outcomes and Choline Levels in Individuals With Obesity: Phase I Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obesity and Obesity-related Medical Conditions
Keywords: Eggs
Liver health
Obesity
Metabolism
Gut microbiome
Lead sponsor: University of Guelph
Sponsor class: OTHER
Collaborators: name: Research Center of the Institut universitaire de cardiologie et de pneumologie de Québec - ULaval
First posted: 2024-11-13
Enrollment: 20
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this research is to determine the effect of additional daily egg intake on metabolic phenotypes and metabolism in the context of obesity.

Detailed description: Choline-derived phosphatidylcholine has diverse functions including being necessary for packaging and exporting triglycerides from the liver. Choline deficiency induces fatty liver, which occurs very commonly in overweight and obesity, emphasizing the importance of choline in lipid metabolism. Studies suggest the role of gut microbiota and host genetics in influencing choline availability, which gut microbes can convert choline to trimethylamine, and hepatically oxidized by flavin monooxygenase 3 to trimethylamine-N-oxide (TMAO), a recently emerged marker of disease. We have recently shown that phosphatidylcholine (the major form of choline in food) leads to higher plasma concentrations of choline without raising TMAO compared to no choline control, which metabolic heterogeneity in TMAO response that appears to be a function of individual gut microbiota composition. However, the effect of phosphatidylcholine on parameters of liver health and function in the context of obesity has not been examined. This study will leverage a whole-food approach using eggs, which are enriched in phosphatidylcholine, as a modulator of metabolic health with a focus on interindividual variation in response.

The study objectives are: 1) determine the effect of additional daily intake of eggs on metabolic outcomes (liver density and enzymes, circulating lipids and glucose levels, body mass index and adiposity); 2) assess the effects of additional daily intake of eggs on levels of choline and downstream metabolites including TMAO; 3) determine the relation between outcome variables in response to additional daily intake of eggs and metabolic modifiers including the gut microbiota composition and genetic polymorphism. To achieve these objectives, Phase I of the larger study will be conducted, which will have multiple "hits" to form the basis of targetable outcomes. Participants will be asked to keep their habitual diet during the 4-week baseline period, followed by 4 weeks of additional daily intake of 3 whole eggs (intervention) then 4 weeks without daily intake of eggs as a washout. Participants will be free-living and will not be supplied with any other food except for the eggs during the intervention period with no restrictions of energy intake. Participants will make clinic visits every 4 weeks for 12 weeks. At their first visit (week 0), before the intervention (week 4), after the intervention (week 8) and after the washout (week 12), participants will arrive overnight-fasted and liver imaging will be performed. Fasting blood will be obtained by a phlebotomist using a standard venipuncture procedure. Anthropometric measures including waist and hip circumferences and BMI will be collected. Participants will also be asked to turn in their fecal sample in a thermos-insulated bag with ice packs. All samples will be de-identified, distributed among storage vials and stored at -80°C until further analyses.

Eligibility criteria: Inclusion Criteria:

* Male or female participant of any race or ethnicity between 30-65 (inclusive) years of age
* BMI \> 30 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 except for eggs that are provided
* Willing to follow the study protocol including maintaining usual lifestyle during the entire study

Exclusion Criteria:

* Age \< 30 or \> 65 years
* BMI \< 30 kg/m2
* Vegans or individuals who do not consume eggs
* Individuals who are currently pregnant or planning to become pregnant during the course of the study; or are currently breastfeeding
* Smokers, users of recreational drugs
* Individuals taking antibiotics or natural health products including prebiotics or probiotics

Primary outcomes:
measure: Liver physical density by imaging technologies
timeFrame: Weeks 0, 4, 8 and 12
measure: Liver morphology as assessed by imaging technologies
timeFrame: Weeks 0, 4, 8 and 12
measure: Concentration of circulating liver enzymes
timeFrame: Weeks 0, 4, 8 and 12
measure: Concentration of circulating lipid markers
timeFrame: Weeks 0, 4, 8 and 12
measure: Concentration of circulating glucose markers
timeFrame: Weeks 0, 4, 8 and 12
measure: Body mass index in kg/m^2
timeFrame: Weeks 0, 4, 8 and 12
measure: Body circumference in metrics
timeFrame: Weeks 0, 4, 8 and 12
Secondary outcomes:
measure: Choline metabolite response
timeFrame: Weeks 0, 4, 8 and 12
measure: Trimethylamine-N-oxide metabolite response
timeFrame: Weeks 0, 4, 8 and 12
measure: Flavin monooxygenase 3 (FMO3) 472 G>A genetic polymorphism
timeFrame: Week 0
measure: Composition of fecal microbiota
timeFrame: Weeks 0, 4, 8 and 12
Other outcomes:
Locations:
city: Quebec City
country: Canada
facility: Research Center of the Institut universitaire de cardiologie et de pneumologie de Québec - ULaval
state: Quebec
Study officials:
References:
citation: Noga AA, Zhao Y, Vance DE. An unexpected requirement for phosphatidylethanolamine N-methyltransferase in the secretion of very low density lipoproteins. J Biol Chem. 2002 Nov 1;277(44):42358-65. doi: 10.1074/jbc.M204542200. Epub 2002 Aug 21.
citation: Hebbard L, George J. Animal models of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2011 Jan;8(1):35-44. doi: 10.1038/nrgastro.2010.191. Epub 2010 Nov 30.
citation: Zeisel SH, Da Costa KA, Franklin PD, Alexander EA, Lamont JT, Sheard NF, Beiser A. Choline, an essential nutrient for humans. FASEB J. 1991 Apr;5(7):2093-8.
citation: Divella R, Mazzocca A, Daniele A, Sabba C, Paradiso A. Obesity, Nonalcoholic Fatty Liver Disease and Adipocytokines Network in Promotion of Cancer. Int J Biol Sci. 2019 Jan 1;15(3):610-616. doi: 10.7150/ijbs.29599. eCollection 2019.
citation: 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.
citation: Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.1056/NEJMoa1109400.
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.