Trimethylamine N-oxide Effects of a Pomegranate Supplement Simultaneously With Carnitine (TESSA)
- Conditions
- Healthy
- Interventions
- Dietary Supplement: L-carnitine + Microcrystalline celluloseDietary Supplement: L-carnitine + Pomegranate extract
- Registration Number
- NCT06518343
- Lead Sponsor
- Quadram Institute Bioscience
- Brief Summary
Trimethylamine N-oxide (TMAO) is produced in some individuals whose diets include meat, fish, and dairy.These foods are rich in L-carnitine. L-carnitine is metabolised by the liver and gut microorganisms (bacteria) into TMAO. In the TESSA study, investigators will explore whether pomegranate extract can lower the production of TMAO in healthy men and women. This reduction in TMAO production has been associated with decreasing a person's risk of heart disease.
- Detailed Description
The TESSA study is a 18 day randomised, double-blind, placebo-controlled two-arm crossover pilot study conducted at the NIHR (National Institute for Health and Care Research) Norfolk Clinical Research Facility (CRF) in the Quadram Institute in Norwich. Investigators are seeking men and women over the age of 18 years who habitually consume meat, fish, and/or eggs and are TMAO producers to determine whether pomegranate extract affects L-carnitine metabolism compared to a matched placebo. This study is conducted in two phases. The first phase involves two study visits where investigators will identify and invite TMAO producing individuals to continue to the second phase of this study. Moreover, investigators will ask the participant to complete a food frequency questionnaire. The second phase involves two intervention periods which are separated by a 10 day washout. Each intervention period begins with a run-in followed by three study visits. Investigators will precisely quantify the absorption (blood plasma concentrations over time, pharmacokinetic study) and metabolism of L-carnitine and its products of metabolism which includes TMAO. Additionally, investigators will examine pomegranate metabolism and excretion with timed urine collections and stool samples.
Participants will consume three L-carnitine capsules at the first visit during the first phase. In the second phase, participants will consume L-carnitine capsules with the intervention capsules (pomegranate extract or placebo) for the first intervention period then after the washout period, participants will crossover and consume L-carnitine capsules with the other intervention capsules for the second intervention period. For each intervention period, three L-carnitine capsules with four intervention capsules at the first visit following the run-in. During the second phase starting at the run-in period participants will be asked to follow a standardized, controlled diet which will be low in choline, L-carnitine, and ellagitannins.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Microcrystalline cellulose L-carnitine + Microcrystalline cellulose 1.5 grams L-carnitine (Carnipure®) + 1.5 grams microcrystalline cellulose (MCC, Redwells Health) in hydroxypropyl methylcellulose (HPMC) capsules Pomegranate extract L-carnitine + Pomegranate extract 1.5 grams L-carnitine (Carnipure®) + 1.6 grams pomegranate extract (Dermogranate®) in hydroxypropyl methylcellulose (HPMC) capsules
- Primary Outcome Measures
Name Time Method Difference in the area under the curve (AUC) of blood plasma TMAO concentrations after pomegranate extract and microcrystalline cellulose interventions. Day 2,3,4,16,17,and 18 Comparison of AUC of blood plasma TMAO concentrations after L-carnitine with pomegranate extract and after L-carnitine with microcrystalline cellulose interventions.
- Secondary Outcome Measures
Name Time Method Change in plasma half-life (t1/2) of L-carnitine and its metabolites 48 hours Plasma blood concentrations of L-carnitine and its metabolites (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) will be quantified after ingestion of L-carnitine and intervention capsules (pomegranate extract or microcrystalline cellulose). Half life will be the time point where concentration of L-carnitine or its metabolites have reduced by half. Measurements will be taken 0, 0.5, 1, 1.5, 2, 2.5, 16, 18, 20, 22, 24, and 48 hours after capsules have been ingested on Day 2 and Day 16.
Changes in gut microbiota composition (indices of diversity and in taxonomic abundances) over study duration Day 2, 4, 16, and 18. Comparison of gut microbiota composition will be determined using indices of diversity and taxonomic abundances using Shotgun metagenomic sequencing of faecal samples collected at the start and end of each intervention period.
Change in the time to reach peak plasma concentration (Tmax) of L-carnitine and its metabolites 48 hours Plasma blood concentrations of L-carnitine and its metabolites (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) will be quantified after ingestion of L-carnitine and intervention capsules (pomegranate extract or microcrystalline cellulose). Tmax will be the time when peak concentration of L-carnitine or its metabolites has been reached. Measurements will be taken 0, 0.5, 1, 1.5, 2, 2.5, 16, 18, 20, 22, 24, and 48 hours after capsules have been ingested on Day 2 and Day 16.
Difference in L-carnitine and its metabolites concentrations from faecal (stool) collections after pomegranate extract and microcrystalline cellulose interventions. Day 2, 4, and 18. Comparison in L-carnitine and and its metabolite (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) excretion into faeces (stool) will be measured from faecal samples at baseline and after each intervention period. These metabolites will be used to define relationships between dietary intake, L-carnitine metabolism and microbiome composition
Change in pomegranate polyphenols and their metabolite concentrations from pooled 24 hour urine collections. Day 3, 4, 17, and 18. Quantification of pomegranate polyphenols and their metabolite excretion into urine will be measured from pooled urine collections (24 and 48 hours) using targeted metabolite analysis of pomegranate polyphenols, punicalagin, ellagic acid, urolithins. These metabolites will be used to define relationships between dietary intake, pomegranate metabolism and pharmacokinetic outcomes
Correlation between plasma TMAO concentration and quantity of L carnitine-rich foods consumed in habitual diets of healthy men and women. Phase 1 Day 2 Plasma TMAO concentration measured during the first phase of this study will be correlated (Pearson correlation) with the quantity of L-carnitine-rich foods collected from a 90-day Food Frequency Questionnaire (VioCare VioScreen).
Treatment effects of gut microbiota composition (indices of diversity and in taxonomic abundances) after pomegranate extract and microcrystalline cellulose interventions. Day 4 and 18. Comparison of gut microbiota composition will be determined using indices of diversity and taxonomic abundances using Shotgun metagenomic sequencing of faecal samples collected at the end of each intervention period.
Changes in area under the curve (AUC) from plasma concentrations of L-carnitine and its metabolites 48 hours Plasma blood concentrations of L-carnitine and its metabolites (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) will be quantified after ingestion of L-carnitine and intervention capsules (pomegranate extract or microcrystalline cellulose). AUC will be determined using trapezoidal approximation of plasma concentrations over time. Measurements will be taken 0, 0.5, 1, 1.5, 2, 2.5, 16, 18, 20, 22, 24, and 48 hours after capsules have been ingested on Day 2 and Day 16.
Change in peak plasma concentration (Cmax) of L-carnitine and its metabolites 48 hours Plasma blood concentrations of L-carnitine and its metabolites (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) will be quantified after ingestion of L-carnitine and intervention capsules (pomegranate extract or microcrystalline cellulose). Cmax will be the highest concentration measured during a 48 hour period. Measurements will be taken 0, 0.5, 1, 1.5, 2, 2.5, 16, 18, 20, 22, 24, and 48 hours after capsules have been ingested on Day 2 and Day 16.
Change in the area under the curve (AUC) from urine concentrations of L-carnitine and its metabolites 48 hours Urine concentrations of L-carnitine and its metabolites (γ-BB: γ-butyrobetaine, TMA: trimethylamine, and TMAO) will be quantified after ingestion of L-carnitine and intervention capsules (pomegranate extract or microcrystalline cellulose). AUC will be determined using trapezoidal approximation of plasma concentrations over time. Measurements will be taken from urine collections at 0, 2, 2.5 to 16, 18, 20, 22, 24, and 24 to 48 hours.
Difference in bacterial transcripts from faecal (stool) collections after pomegranate extract and microcrystalline cellulose interventions. Day 2, 4, and 18. Comparison of absolute abundance of L-carnitine metabolising bacterial genes and their transcripts using specific qPCR (quantitative polymerase chain reaction) and RT-qPCR (Real-time polymerase chain reaction) assays from faecal samples collected at baseline and after each intervention period.
Trial Locations
- Locations (1)
Quadram Institute
🇬🇧Norwich, Norfolk, United Kingdom