Clinical Trial: Vitamin B6 Dependence of One-Carbon Metabolism

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Vitamin B6 Dependence of One-Carbon Metabolism

Brief Summary: Marginal vitamin B6 deficiency, which occurs commonly worldwide, leads to a cellular deficiency of the coenzyme pyridoxal phosphate (PLP). PLP is a coenzyme in several phases of one carbon (1C) metabolism, which is the array of reactions in which one carbon units are acquired and used in reactions including nucleotide synthesis, regeneration of methionine (Met) from homocysteine (Hcy), and methylation of many biological compounds. 1C metabolism is linked to the transsulfuration pathway in which Hcy undergoes PLP-dependent catabolism leading to cysteine, whose availability governs the formation of the antioxidant glutathione. Nutritional or genetic conditions that impair 1C metabolism are associated with elevation in plasma Hcy concentration and increased risk of vascular disease. It is believed that the metabolic effects of vitamin B6 deficiency will be most pronounced following protein intake when the vitamin B6-dependent pathways of amino acid metabolism experience the greatest substrate load. The human subjects protocols of this study consist of two distinct phases intended to extend our understanding of basic human 1C metabolism and the effects of marginal vitamin B6 deficiency under postprandial conditions. Phase 1 will investigate the effects of vitamin B6 nutrition on the PLP-dependent generation of 1C units by the glycine cleavage system and on the synthesis of glutathione. Phase 2 will investigate the dependence of methionine metabolism on vitamin B6 nutritional status, with particular emphasis on the recycling of Hcy to Met. Each phase of this study will involve 14 healthy, nutritionally adequate, young adults (7 male, 7 female) who will undergo metabolite profiling and kinetic analysis using intravenously infused stable isotopic tracers performed both before and after a ~4-week period of dietary vitamin B6 restriction. Subjects will be assigned to either Phase 1 or Phase 2, which will be identical in design except for the tracers and analytical methods us

Detailed Summary:

If you volunteer for this study, you will come to the General Clinical Research Center (GCRC) at Shands Hospital for a screening visit. There approximately 27.5 mL of blood (5 1/2 teaspoons) will be taken from a vein in your arm. This will be used for tests to determine whether you are receiving adequate amounts of vitamin B6 and other vitamins, to analyze a part of the genetic information in certain blood cells that relates to how your body processes some nutrients, and to confirm your general health. If the vitamin B6 content of your blood is higher than the range needed for this study, which sometimes occurs from eating fortified foods, you might be asked to give another blood sample (2 teaspoons) after several weeks to have the screening test repeated. You will also be asked questions about your health and a detailed assessment of your regular diet will be carried out. Your general health will be confirmed by taking a medical history, physical exam, and standard blood tests including liver, kidney, bone marrow function, cholesterol and urine analysis. To take part in this study, you must be in good health and in adequate nutritional status for vitamin B6 and other vitamins.

Because of risks to a developing fetus from inadequate vitamin B6 intake, a pregnancy test will be conducted with females three times during the study (during the screening visit and before each hospital admission) and women who participate in this study should use protection to prevent pregnancy during the study; if you become pregnant you will be released from the study.

Once you have completed all screening procedures you will be asked to eat meals prepared by the GCRC for 2 days, you will then participate in the procedure to test how effectively vitamin B6 functions in helping your body use certain amino acids. This will involve giving you a sol
Sponsor: University of Florida

Current Primary Outcome:

• 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

Original Primary Outcome: No direct subject benefit; study is to gain information relevant to health. The results of this study will be beneficial to the population as a whole, and this benefit outweighs the low risks. [ Time Frame: One year ]

Current Secondary Outcome: Hypotheses Aim 3 [ Time Frame: 30 days ]

Original Secondary Outcome:

Information By: University of Florida

Dates:
Date Received: April 1, 2009
Date Started: January 2008
Date Completion:
Last Updated: March 25, 2013
Last Verified: March 2013