Vitamin B6 Dependence of One-Carbon Metabolism
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00877812|
Recruitment Status : Completed
First Posted : April 8, 2009
Last Update Posted : March 27, 2013
|Condition or disease||Intervention/treatment||Phase|
|Vitamin B6 Deficiency||Dietary Supplement: Arm 1 glycine and leucine Dietary Supplement: Arm 2 Intervention of Serine and methionine infusion||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Vitamin B6 Dependence of One-Carbon Metabolism|
|Study Start Date :||January 2008|
|Actual Primary Completion Date :||September 2010|
|Actual Study Completion Date :||September 2010|
Experimental: Arm 1 glycine and leucine infusion
Determine in healthy, adequately pyridoxine nourished humans using a protocol based on amino acid glycine tracer methods: (a) the postprandial rates of in vivo glycine turnover, glycine-based generation of one-carbon units, thymidylate and purine synthesis, and the impact of vitamin B6 deficiency on the rates of these processes and (b) the effect of vitamin B6 deficiency on the postprandial rate of glutathione synthesis. 14 subjects will be chosen after screening is complete and will begin a B6 deficient diet for 30 days. At the beginning and end of the 30 days they will receive an infusion of leucine and glycine then they will begin the four week diet. At the end of four weeks the infusion will be repeated.
Dietary Supplement: Arm 1 glycine and leucine
Arm 1 glycine and leucine: A subset of 14 participants out of the total enrolled participants with an adequate nutritional status will undergo the tracer infusion of glycine and leucine amino acids protocol while an adequate vitamin pyridoxine, B6 status. After the first infusion each participant will then begin a diet low in vitamin B6 (<0.5 mg/d) for 4 weeks to achieve marginal B6 status followed by a repeat of fasting blood sampling and tracer infusion protocol.
Experimental: Arm 2 Intervention of Serine and methionine infusion
This arm will allow investigation of total Hcy remethylation and remethylation from serine-derived 1C units, kinetics of serine and the methionine cycle and kinetics of transsulfuration reactions. 14 healthy subjects will be selected and screened. Prior to starting a B6 deficient diet for four weeks an infusion of serine and methionine will commence. Following the first infusion the diet will begin and after four weeks another infusion will be done.
Dietary Supplement: Arm 2 Intervention of Serine and methionine infusion
Arm 2 Intervention of Serine and methionine infusion: A subset of 14 participants out of the total enrolled participants. Received an adequate nutritional status will undergo the tracer infusion of methionine and serine amino acids protocol while in adequate vitamin pyridoxine, B6 status. After the first infusion each subject will then begin a diet low in vitamin B6 (<0.5 mg/d) for 4 weeks to achieve marginal B6 status followed by repeat of fasting blood sampling and tracer infusion protocol.
- Hypothesis Aim 1 [ Time Frame: One year ](a) Vitamin B6 deficiency will reduce the rate of glycine turnover and interconversion with serine and will reduce the generation of 1C units by the glycine cleavage system. (b) Vitamin B6 deficiency will yield a reduced in vivo rate of erythrocyte glutathione synthesis.
- Hypotheses Aim 2 [ Time Frame: 30 days ](a) Vitamin B6 deficiency will reduce the in vivo rate of generation of one-carbon units from serine and, thus, overall homocysteine remethylation. (b) In vivo rates of cysteine synthesis will be reduced in vitamin B6 deficiency. (c) Thymidylate synthesis from serine-derived one-carbon units will be reduced during vitamin B6 deficiency
- Hypotheses Aim 3 [ Time Frame: 30 days ](a) Vitamin B6 deficiency will yield increased plasma glycine, cystathionine and glutathione but decreased erythrocyte glutathione concentration. (b) Vitamin B6 deficiency will cause reduced activity of lymphocyte SHMT and the glycine cleavage system and reduced cellular (lymphocyte) glycine concentration..
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00877812
|United States, Florida|
|University of Florida|
|Gainesville, Florida, United States, 32611|
|Principal Investigator:||Jesse F Gregory, PhD||University of Florida|