The Effects of 8-week Choline, Betaine, and Folic Acid Supplementation on Plasma Homocysteine Concentration During Guanidinoacetic Acid Loading in Young Healthy Volunteers

Study Overview
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Brief Summary
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A methyl-group acceptor such as guanidinoacetic acid (GAA) could induce hyperhomocysteinemia with the effects of GAA expected to be dose-dependent. Due to the fact that hyperhomocysteinemia is thought to be an independent risk factor for cardiovascular and neurodegenerative diseases, different dietary agents were used in the past for the treatment of elevated total plasma homocysteine (T-HCy), e. g. betaine, choline (betaine precursor) or folic acid. In the context of GAA loading the question arises whether intake of betaine, choline (betaine precursor) or folic acid during GAA loading could affect plasma T-HCy in healthy humans. Forty healthy physically active men and women aged 20 to 30 years will take part in this GAA-controlled, double-blind and parallel-group intervention study. Subjects will be allocated to four randomly assigned trials, with treatment lasting for 8 weeks and washout period of 28 days. The 4 test treatment-groups will include TEST1 (GAA only), TEST2 (GAA, choline, B6, B12 and folic acid), TEST3 (GAA, betaine, B6, B12 and folic acid) and TEST4 (GAA, B6, B12 and folic acid). Plasma T-HCy will be the primary outcome measure assessed every second week throughout the study. Plasma B-vitamins and blood and urine metabolites (GAA, creatine, methionine, arginine) will be secondary outcome measures along with adverse-effects indicators assessed every second week throughout the study. Selected body composition indicators will be obtained at 0, 2, 8 and 12 weeks throughout the study to monitor the effects of experimental treatments on body hydration and protein synthesis. This research will test the hypothesis that a combination of GAA with homocysteine lowering nutrients attenuates the elevation of T-hcy, and will further display the size-effect of each additive used.

Conditions
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Hyperhomocysteinemia

Intervention / Treatment
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* Drug: TEST 1
* Drug: TEST 2
* Drug: TEST 3
* Drug: TEST 4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy male and non-pregnant females moderately physically active aged 20 to 30 years not currently taking any dietary supplement for the past 2 months Exclusion Criteria: - total plasma homocysteine above 15.5 µmol/L

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEST1<br>2.4 g/day of guanidinoacetic acid | Drug: TEST 1<br>* 2.4 g/day of guanidinoacetic acid<br>|
| Experimental: TEST 2<br>2.4 g/day of guanidinoacetic acid + 3.0 g/day of choline dihydrogen citrate + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid | Drug: TEST 2<br>* 2.4 g/day of guanidinoacetic acid + 3.0 g/day of choline dihydrogencitrate + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid<br>|
| Experimental: TEST 3<br>2.4 g/day of guanidinoacetic acid + 1.6 g/day of betaine HCl + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid | Drug: TEST 3<br>* 2.4 g/day of guanidinoacetic acid + 1.6 g/day of betaine HCl + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid<br>|
| Experimental: TEST 4<br>2.4 g/day of guanidinoacetic acid + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid | Drug: TEST 4<br>* 2.4 g/day of guanidinoacetic acid + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total plasma homocysteine |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum creatine |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remethylation, Human Subjects, Clinical Trial, B-vitamin, Creatine