Trial Outcomes & Findings for Choline Nutritional Status: Development of a Biomarker Panel (NCT NCT03726671)
NCT ID: NCT03726671
Last Updated: 2023-01-06
Results Overview
The liver choline pool determined by the dilution of the deuterated choline metabolites formed in liver and released to plasma as measured by isotopic enrichment ratio (IER). The IER for a given metabolite is defined as the concentration of a deuterated metabolite divided by the sum of deuterated and non-deuterated metabolite.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
101 participants
Primary outcome timeframe
24 hours following administration of choline-d9 on day 12 of respective dietary intervention
Results posted on
2023-01-06
Participant Flow
Participant milestones
| Measure |
25%Cho, 50%Cho, 100%Cho
Diets containing 137.5 mg (25% Cho diet), 275 mg (50% Cho diet), and 550 mg (100% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
|
25% Cho, 100% Cho, 50% Cho
Diets containing 137.5 mg (25% Cho diet) , 550 mg (100% Cho diet), and 275 mg Cho (50% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
|
50% Cho, 25% Cho, 100% Cho
Diets containing 275 mg (50% Cho diet), 137.5 mg (25% Cho diet), and 550 mg Cho (100% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
|
50% Cho, 100% Cho, 25% Cho
Diets containing 275 mg (50% Cho diet), 550 mg (100% Cho diet), and 137.5 mg Cho (25% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
|
100% Cho, 25% Cho, 50% Cho
Diets containing 550 mg (100% Cho diet), 137.5 mg (25% Cho diet), and 275 mg Cho (50% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
|
100% Cho, 50% Cho, 25% Cho
Diets containing 550 mg (100% Cho diet), 275 mg (50% Cho diet), and 137.5 mg Cho (25% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus
|
|---|---|---|---|---|---|---|
|
First Intervention (2 Weeks)
STARTED
|
27
|
14
|
14
|
13
|
24
|
9
|
|
First Intervention (2 Weeks)
COMPLETED
|
20
|
12
|
12
|
12
|
19
|
8
|
|
First Intervention (2 Weeks)
NOT COMPLETED
|
7
|
2
|
2
|
1
|
5
|
1
|
|
Washout (>/= 2 Weeks)
STARTED
|
17
|
12
|
12
|
11
|
18
|
8
|
|
Washout (>/= 2 Weeks)
COMPLETED
|
17
|
12
|
12
|
11
|
17
|
8
|
|
Washout (>/= 2 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Second Intervention (2 Weeks)
STARTED
|
20
|
12
|
12
|
12
|
19
|
8
|
|
Second Intervention (2 Weeks)
COMPLETED
|
17
|
12
|
12
|
11
|
18
|
8
|
|
Second Intervention (2 Weeks)
NOT COMPLETED
|
3
|
0
|
0
|
1
|
1
|
0
|
|
Third Intervention (2 Weeks)
STARTED
|
17
|
12
|
12
|
11
|
17
|
8
|
|
Third Intervention (2 Weeks)
COMPLETED
|
17
|
11
|
12
|
11
|
17
|
8
|
|
Third Intervention (2 Weeks)
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Choline Nutritional Status: Development of a Biomarker Panel
Baseline characteristics by cohort
| Measure |
Total Number of Participants
n=101 Participants
All participants who were randomly assigned to diet sequence containing 137.5 mg (25% Cho diet), 275 mg (50% Cho diet), and 550 mg (100% Cho diet) for two weeks each with 2 weeks of washout between.
|
|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
100 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
|
Sex: Female, Male
Female
|
71 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
92 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
13 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
85 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
101 Participants
n=93 Participants
|
|
Menopausal Status
Pre-Menopausal Females
|
50 Participants
n=93 Participants
|
|
Menopausal Status
Post-Menopausal Females
|
21 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 24 hours following administration of choline-d9 on day 12 of respective dietary interventionPopulation: Participants who completed at least 2 arms were included in the analysis. Out of 101 randomized, 78 met this criteria. Of the 78, 3 were excluded for noncompliance, leaving 75 participants. Of these 75, 75 completed the 25%, 73 completed the 50% \& 75 completed the 100% diets. One participant completing 3 arms was missing 50% isotope dilution data; consequently, outcomes analyzed for 75 participants (25%), 72 participants (50%), \& 75 participants (100%).
The liver choline pool determined by the dilution of the deuterated choline metabolites formed in liver and released to plasma as measured by isotopic enrichment ratio (IER). The IER for a given metabolite is defined as the concentration of a deuterated metabolite divided by the sum of deuterated and non-deuterated metabolite.
Outcome measures
| Measure |
25% Cho
n=75 Participants
Diet containing 137.5 mg (25% Cho diet) given for two weeks with =/\> 2 weeks of washout.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho
n=72 Participants
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho
n=75 Participants
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CC
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CC genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, GG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have GG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CC
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CC genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, GG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have GG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
|---|---|---|---|---|---|---|---|---|---|
|
Ratio of Liver Choline Pool Size by Isotope Dilution
Betaine IER
|
0.02357 isotopic enrichment ratio
Standard Deviation 0.00802
|
0.02403 isotopic enrichment ratio
Standard Deviation 0.00882
|
0.02184 isotopic enrichment ratio
Standard Deviation 0.00574
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Ratio of Liver Choline Pool Size by Isotope Dilution
Choline IER
|
0.00023 isotopic enrichment ratio
Standard Deviation 0.00511
|
0.00132 isotopic enrichment ratio
Standard Deviation 0.00493
|
0.00191 isotopic enrichment ratio
Standard Deviation 0.00399
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Ratio of Liver Choline Pool Size by Isotope Dilution
Phosphatidylcholine IER
|
0.01158 isotopic enrichment ratio
Standard Deviation 0.00326
|
0.01130 isotopic enrichment ratio
Standard Deviation 0.00324
|
0.01017 isotopic enrichment ratio
Standard Deviation 0.00234
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: At the end of 2 weeks of respective Cho dietPopulation: Participants who completed at least 2 arms were included in the analysis. Out of 101 randomized, 78 met this criteria. Of the 78, 3 were excluded for noncompliance, leaving 75 participants. Of these 75, 75 completed the 25%, 73 completed the 50% \& 75 completed the 100% diets.
Plasma choline metabolites (micromolar): choline, dimethylglycine, betaine, phosphatidylcholine, sphingomyelin, trimethylamine-oxide, and homocysteine measured by targeted metabolomic profiling. The signature for choline deficiency is defined by choline \<0.793 mmol/L or betaine \<34.9 mmol/L. The levels of these metabolites at the end of each intervention will be compared. The association between choline metabolites and choline pool size will be investigated.
Outcome measures
| Measure |
25% Cho
n=75 Participants
Diet containing 137.5 mg (25% Cho diet) given for two weeks with =/\> 2 weeks of washout.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho
n=73 Participants
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho
n=75 Participants
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CC
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CC genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, GG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have GG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CC
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CC genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, GG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have GG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
|---|---|---|---|---|---|---|---|---|---|
|
Difference in Choline Deficiency Signature
|
57 percentage participants with signature
|
47 percentage participants with signature
|
23 percentage participants with signature
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 24 hours following administration of choline-d9 on day 12 of 25% Cho dietPopulation: Participants who completed at least 2 arms were included in the analysis. Out of 101 randomized, 78 met this criteria. Of the 78, 3 were excluded for noncompliance, leaving 75 participants. All 75 participants completed 25% Cho diet. Only data from the 25% Cho diet (choline depleted state) were analyzed.
The 25% Cho arm was selected because only at that intake level is sufficient depletion achieved. Participants with plasma choline \<0.793 mmol/L or betaine \<34.9 mmol/L were considered as choline depleted (showing signature), participants with plasma choline \>=0.793 mmol/L and betaine \>=34.9 mmol/L were considered as not choline depleted (not showing signature). Available choline pool size was determined by the dilution of the deuterated choline metabolites formed in liver and released to plasma as measured by isotopic enrichment ratio (IER). The IER for a given metabolite is defined as the concentration of a deuterated metabolite divided by the sum of deuterated and non-deuterated metabolite.
Outcome measures
| Measure |
25% Cho
n=57 Participants
Diet containing 137.5 mg (25% Cho diet) given for two weeks with =/\> 2 weeks of washout.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho
n=18 Participants
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CC
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CC genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, GG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have GG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CC
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CC genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, GG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have GG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
|---|---|---|---|---|---|---|---|---|---|
|
Comparison of Choline Pool Size Between Participants With and Without Choline Metabolites Signature During Cho Depletion
Betaine IER
|
0.0234 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0087
|
0.0241 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0057
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Comparison of Choline Pool Size Between Participants With and Without Choline Metabolites Signature During Cho Depletion
Choline IER
|
-0.0005 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0049
|
0.0025 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0051
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Comparison of Choline Pool Size Between Participants With and Without Choline Metabolites Signature During Cho Depletion
Phosphatidylcholine IER
|
0.0115 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0034
|
0.0118 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0030
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: At the end of 2 weeks of respective Cho dietPopulation: Participants who completed at least 2 arms were included in the analysis. Out of 101 randomized, 78 met this criteria. Of the 78, 3 were excluded for noncompliance, leaving 75 participants. Of these 75, 75 completed the 25%, 73 completed the 50% \& 75 completed the 100% diets.
Metabolomics was conducted on plasma that was collected from individuals at the end of each 2-week diet period. UHPLC High Resolution Mass Spectrometry was used for differential profiling (PMID: 33415121). Supervised Orthogonal Partial Least Squares Discriminant Analysis was used to determine signals that differentiated the 25% choline dietary group from the 100% choline dietary group. Metabolites that differentiated the 25% and 100% choline dietary groups with variable importance to projection (VIP) \>1 and p-value \< 0.05 are reported. The signals for these metabolites were matched by retention time, exact mass, and MS/MS to standards run on the same platform. Because this is a differential profiling method (not quantitative), the mean and standard deviation of peak intensities detected on the untargeted platform are reported. Results are reported for the selected metabolites for the 25%, 50%, and 100% choline dietary groups. Ratios can be obtained by division of the intensity data.
Outcome measures
| Measure |
25% Cho
n=75 Participants
Diet containing 137.5 mg (25% Cho diet) given for two weeks with =/\> 2 weeks of washout.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho
n=73 Participants
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho
n=75 Participants
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CC
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CC genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, GG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have GG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CC
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CC genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, GG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have GG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
|---|---|---|---|---|---|---|---|---|---|
|
Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet
L-Carnitine
|
1228784.33 Ion abundance (intensity)
Standard Deviation 306909.00
|
1178435.52 Ion abundance (intensity)
Standard Deviation 316249.45
|
1012630.35 Ion abundance (intensity)
Standard Deviation 344564.26
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet
Propionylcarnitine
|
104096.43 Ion abundance (intensity)
Standard Deviation 39621.16
|
99820.22 Ion abundance (intensity)
Standard Deviation 48710.67
|
80011.86 Ion abundance (intensity)
Standard Deviation 38878.77
|
—
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—
|
—
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—
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—
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—
|
|
Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet
Valerylcarnitine
|
94263.17 Ion abundance (intensity)
Standard Deviation 36626.32
|
93531.64 Ion abundance (intensity)
Standard Deviation 44570.42
|
82582.08 Ion abundance (intensity)
Standard Deviation 40040.76
|
—
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—
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—
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—
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—
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—
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|
Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet
Gamma-Muricholic Acid
|
4285.05 Ion abundance (intensity)
Standard Deviation 5853.57
|
4927.62 Ion abundance (intensity)
Standard Deviation 6834.32
|
2519.32 Ion abundance (intensity)
Standard Deviation 4817.63
|
—
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—
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—
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—
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—
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—
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|
Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet
Kynurenate
|
3200.20 Ion abundance (intensity)
Standard Deviation 1562.40
|
3186.66 Ion abundance (intensity)
Standard Deviation 1405.28
|
2739.41 Ion abundance (intensity)
Standard Deviation 1362.30
|
—
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—
|
—
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—
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—
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—
|
|
Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet
N-Acetylglycine
|
32411.20 Ion abundance (intensity)
Standard Deviation 33107.90
|
28421.55 Ion abundance (intensity)
Standard Deviation 27012.58
|
26644.26 Ion abundance (intensity)
Standard Deviation 26448.88
|
—
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—
|
—
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—
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—
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—
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|
Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet
Deoxycholic Acid
|
731438.14 Ion abundance (intensity)
Standard Deviation 633205.40
|
802858.85 Ion abundance (intensity)
Standard Deviation 772625.96
|
600931.15 Ion abundance (intensity)
Standard Deviation 509303.07
|
—
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—
|
—
|
—
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—
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—
|
|
Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet
L-Ornithine
|
2696.01 Ion abundance (intensity)
Standard Deviation 1213.20
|
2684.53 Ion abundance (intensity)
Standard Deviation 1338.50
|
2410.86 Ion abundance (intensity)
Standard Deviation 1223.70
|
—
|
—
|
—
|
—
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—
|
—
|
|
Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet
Methylimidazoleacetic Acid
|
9875.65 Ion abundance (intensity)
Standard Deviation 6304.32
|
10075.93 Ion abundance (intensity)
Standard Deviation 5111.30
|
8510.57 Ion abundance (intensity)
Standard Deviation 4212.85
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet
N6-Acetyl-L-lysine
|
24100.04 Ion abundance (intensity)
Standard Deviation 7506.44
|
24361.81 Ion abundance (intensity)
Standard Deviation 7273.97
|
22522.45 Ion abundance (intensity)
Standard Deviation 5552.79
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet
DL-2-Aminoadipic Acid
|
3088.49 Ion abundance (intensity)
Standard Deviation 1065.78
|
3065.37 Ion abundance (intensity)
Standard Deviation 1168.13
|
2805.00 Ion abundance (intensity)
Standard Deviation 981.61
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 24 hours following administration of choline-d9 on day 12 of respective dietary interventionPopulation: Participants who completed at least 2 arms were included in the analysis. Out of 101 randomized, 78 met this criteria. Of the 78, 3 were excluded for noncompliance. Of the 75 remaining, one had missing SNP data. One had missing isotope dilution data in 50% Cho. Two subjects did not complete 50% Cho. That brings the sample size down to 74, 71, and 74 for the 25%, 50%, and 100%, respectively. Overall Number of Participants Analyzed includes Pre- and Post-Menopausal Females \& Males.
DNA was collected and evaluated for the presence of the PEMT SNP rs12325817. Genotypes was measured by real time polymerase chain reaction (RT-PCR). The magnitude of changes in choline pool size as measured by IER at the end of each dietary intervention was compared among subjects with different genotypes in the PEMT SNP. Linear mixed model with repeated measures was performed for each group (healthy males, pre- and postmenopausal females) separately to study the genotype effect and genotype x diet interaction effect on choline pool size.
Outcome measures
| Measure |
25% Cho
n=17 Participants
Diet containing 137.5 mg (25% Cho diet) given for two weeks with =/\> 2 weeks of washout.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho
n=34 Participants
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho
n=23 Participants
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CC
n=16 Participants
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CC genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CG
n=34 Participants
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, GG
n=21 Participants
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have GG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CC
n=17 Participants
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CC genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CG
n=34 Participants
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, GG
n=23 Participants
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have GG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
|---|---|---|---|---|---|---|---|---|---|
|
Comparison of Choline Pool Size Between Participants With Different Genotypes in Phosphatidylethanolamine-N-methyltransferase (PEMT) Single Nucleotide Polymorphism (SNP rs12325817)
Pre-Menopausal Females: Betaine IER
|
0.0259 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0101
|
0.0201 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.01
|
0.0261 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0064
|
0.0244 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0073
|
0.0224 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0059
|
0.0262 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0073
|
0.0243 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0072
|
0.0213 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0046
|
0.0247 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0039
|
|
Comparison of Choline Pool Size Between Participants With Different Genotypes in Phosphatidylethanolamine-N-methyltransferase (PEMT) Single Nucleotide Polymorphism (SNP rs12325817)
Pre-Menopausal Females: Choline IER
|
-0.0018 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0051
|
-0.0018 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0063
|
-0.0011 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0028
|
-0.0004 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0051
|
0.0004 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0054
|
-0.0007 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0036
|
0.0004 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0044
|
0.0008 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0042
|
0.0001 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0039
|
|
Comparison of Choline Pool Size Between Participants With Different Genotypes in Phosphatidylethanolamine-N-methyltransferase (PEMT) Single Nucleotide Polymorphism (SNP rs12325817)
Pre-Menopausal Females: Phosphatidylcholine IER
|
0.0113 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.003
|
0.011 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0044
|
0.011 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0024
|
0.011 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0027
|
0.011 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0032
|
0.0115 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0033
|
0.0107 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0024
|
0.0105 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0025
|
0.01 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0017
|
|
Comparison of Choline Pool Size Between Participants With Different Genotypes in Phosphatidylethanolamine-N-methyltransferase (PEMT) Single Nucleotide Polymorphism (SNP rs12325817)
Post-Menopausal Females: Betaine IER
|
0.0212 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.007
|
0.02 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0033
|
0.0265 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0124
|
0.0136 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0126
|
0.0212 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0026
|
0.028 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0127
|
0.0232 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0037
|
0.0175 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0026
|
0.02 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0086
|
|
Comparison of Choline Pool Size Between Participants With Different Genotypes in Phosphatidylethanolamine-N-methyltransferase (PEMT) Single Nucleotide Polymorphism (SNP rs12325817)
Post-Menopausal Females: Choline IER
|
0.0014 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0048
|
-0.0001 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0039
|
0.0017 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.005
|
0.0006 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0084
|
0.0007 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0042
|
0.0044 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0045
|
0.0047 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0022
|
0.0019 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0027
|
0.0026 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0035
|
|
Comparison of Choline Pool Size Between Participants With Different Genotypes in Phosphatidylethanolamine-N-methyltransferase (PEMT) Single Nucleotide Polymorphism (SNP rs12325817)
Post-Menopausal Females: Phosphatidylcholine IER
|
0.0095 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0021
|
0.009 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0014
|
0.0127 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0043
|
0.0071 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0049
|
0.01 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.001
|
0.0121 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0041
|
0.0096 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0016
|
0.0086 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0011
|
0.0096 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0023
|
|
Comparison of Choline Pool Size Between Participants With Different Genotypes in Phosphatidylethanolamine-N-methyltransferase (PEMT) Single Nucleotide Polymorphism (SNP rs12325817)
Males: Betaine IER
|
0.0264 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0059
|
0.025 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0053
|
0.024 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0045
|
0.0419 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0264
|
0.0241 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0045
|
0.0222 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0021
|
0.0247 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0053
|
0.0201 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0077
|
0.0213 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0036
|
|
Comparison of Choline Pool Size Between Participants With Different Genotypes in Phosphatidylethanolamine-N-methyltransferase (PEMT) Single Nucleotide Polymorphism (SNP rs12325817)
Males: Choline IER
|
0.0043 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0026
|
0.0029 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0034
|
0.003 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0061
|
0.0097 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0022
|
0.0028 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0026
|
0.0029 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0045
|
0.0061 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0005
|
0.0029 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0038
|
0.0041 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0042
|
|
Comparison of Choline Pool Size Between Participants With Different Genotypes in Phosphatidylethanolamine-N-methyltransferase (PEMT) Single Nucleotide Polymorphism (SNP rs12325817)
Males: Phosphatidylcholine IER
|
0.0131 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0002
|
0.0135 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0021
|
0.013 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0027
|
0.0184 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0034
|
0.0111 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0019
|
0.0123 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0016
|
0.0127 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0007
|
0.0094 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0035
|
0.0112 isotopic enrichment ratio (uM/uM)
Standard Deviation 0.0012
|
PRIMARY outcome
Timeframe: Day 1 and Day 15 of respective Cho dietPopulation: Participants who completed at least 2 arms were included in the analysis. Out of 101 randomized, 78 met this criteria. Of the 78, 3 were excluded for noncompliance, leaving 75 participants. Of these 75, 75 completed the 25%, 73 completed the 50% \& 75 completed the 100% diets. Fibroscan data were missing for 2 participants in the 25% Cho arm and 2 in the 50% arm.
Controlled attenuation parameter (CAP) as measured by Fibroscan is an ultrasound-based technique to measure liver fat. This method will be used with other biomarkers to indicate functional signs of choline status.
Outcome measures
| Measure |
25% Cho
n=73 Participants
Diet containing 137.5 mg (25% Cho diet) given for two weeks with =/\> 2 weeks of washout.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho
n=71 Participants
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho
n=75 Participants
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CC
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CC genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, GG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have GG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CC
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CC genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, GG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have GG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
|---|---|---|---|---|---|---|---|---|---|
|
Change in Liver Fat Content Based on CAP Values
|
0.0208 dB/m
Standard Deviation 0.1513
|
0.6958 dB/m
Standard Deviation 0.2144
|
0.0135 dB/m
Standard Deviation 0.1482
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At the end of 2 weeks of respective Cho dietPopulation: MRS was run on only an initial 40 participants due to limited funding. Due to extensive variation, MRS data were not usable for 8 participants in the 25%, 10 participants in the 50%, and 8 participants in the 100% Cho arms.
MRS is a direct measurement of liver choline content. Changes in liver choline by MRS should correlate with changes in liver choline inferred by calculation of isotope enrichment ratio (IER) of plasma metabolites. Pearson correlation coefficient used to study the correlation between data generated from the two types of measurements.
Outcome measures
| Measure |
25% Cho
n=32 Participants
Diet containing 137.5 mg (25% Cho diet) given for two weeks with =/\> 2 weeks of washout.
25% Cho diet: Subjects will consume meals containing 25% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho
n=30 Participants
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho
n=32 Participants
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CC
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CC genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, CG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have CG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
50% Cho, rs12325817, GG
Diet containing 275 mg Cho (50% Cho diet) given for two weeks with =/\> 2 weeks of washout. These participants have GG genotype.
50% Cho diet: Subjects will consume meals containing 50% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CC
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CC genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, CG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have CG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
100% Cho, rs12325817, GG
Diet containing 550 mg Cho (100% Cho diet) given for two weeks each with =/\> 2 weeks of washout. These participants have GG genotype.
100% Cho diet: Subjects will consume meals containing 100% of recommended intake of Choline for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride (trimethyl-d9, 9%) as a bolus.
|
|---|---|---|---|---|---|---|---|---|---|
|
Validation of Isotope Dilution Method to Assess Choline Pool Size by Magnetic Resonance Spectroscopy (MRS)
|
8.4 mM
Standard Deviation 4.1
|
7.8 mM
Standard Deviation 4.5
|
11.2 mM
Standard Deviation 7.2
|
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OTHER_PRE_SPECIFIED outcome
Timeframe: At baseline visitExploratory analysis of \>2 million SNPs measured on a custom Illumina Expanded Multi-Ethnic genotyping array (Mega-Ex). The same analysis described for Outcome 4 will be applied for Outcome 7. Benjamini-Hochberg method for False Discovery Rate (FDR) correction will be used for multiple testing correction.
Outcome measures
Outcome data not reported
Adverse Events
25% Cho
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
50% Cho
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
100% Cho
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Julie M. Stegall, MSW
University of North Carolina at Chapel Hill
Phone: 704-250-5048
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place