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

Hyperhomocysteinemia Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01371357
• Other study ID #: BN-214E-S10
• Status: Completed
• Phase: Phase 3
• First received: June 9, 2011
• Last updated: December 18, 2011
• Start date: May 2011
• Est. completion date: December 2011

Study information

• Verified date: December 2011
• Source: Center for Health, Exercise and Sport Sciences, Serbia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Serbia: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 30 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyperhomocysteinemia

Intervention

Drug:
• TEST 1
2.4 g/day of guanidinoacetic acid
• TEST 2
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
• TEST 3
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
• TEST 4
2.4 g/day of guanidinoacetic acid + 5 µg/day of B12 + 10 mg/day of B6 + 600 µg/day of folic acid

Locations

Country	Name	City	State
Serbia	Center for Health, Exercise and Sport Sciences	Belgrade

Sponsors (1)

Lead Sponsor	Collaborator
Center for Health, Exercise and Sport Sciences, Serbia

Country where clinical trial is conducted

Serbia, 

References & Publications (3)

Olthof MR, Brink EJ, Katan MB, Verhoef P. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr. 2005 Jul;82(1):111-7. — View Citation

Setoue M, Ohuchi S, Morita T, Sugiyama K. Hyperhomocysteinemia induced by guanidinoacetic acid is effectively suppressed by choline and betaine in rats. Biosci Biotechnol Biochem. 2008 Jul;72(7):1696-703. Epub 2008 Jul 7. — View Citation

Verhoef P, de Groot LC. Dietary determinants of plasma homocysteine concentrations. Semin Vasc Med. 2005 May;5(2):110-23. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total plasma homocysteine		3 months	Yes
Secondary	Serum creatine		3 months	Yes

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