title: One-carbon metabolites and telomere length in a prospective and randomized study of B- and/or D-vitamin supplementation.
abstract: BACKGROUND
  Vitamin B deficiency is common in elderly people and has been associated with an increased risk of developing age-related diseases. B-vitamins are essential for the synthesis and stability of DNA. Telomers are the end caps of chromosomes that shorten progressively with age, and short telomers are associated with DNA instability.
  
  
  OBJECTIVE
  In the present randomized intervention study, we investigated whether the one-carbon metabolism is related to telomere length, a surrogate marker for cellular aging.
  
  
  METHODS
  Sixty-five subjects (>54 years) were randomly assigned to receive either a daily combination of vitamin D3 (1200 IU), folic acid (0.5 mg), vitamin B12(0.5 mg), vitamin B6(50 mg) and calcium carbonate (456 mg) (group A) or vitamin D3 and calcium carbonate alone (group B). Blood testing was performed at baseline and after 1 year of supplementation. The concentrations of several metabolites of the one-carbon pathway, as well as relative telomere length (RTL) and 5,10-methylenetetrahydrofolate reductase C677T genotype, were analyzed.
  
  
  RESULTS
  At baseline, age- and gender-adjusted RTL correlated with total folate and 5-methyltetrahydrofolate (5-methylTHF). Subjects with RTL above the median had higher concentrations of total folate and 5-methylTHF compared to subjects below the median. At study end, gender- and age-adjusted RTL correlated in group A with methylmalonic acid (MMA; r = -0.460, p = 0.0012) and choline (r = 0.434, p = 0.0021) and in group B with 5,10-methenyltetrahydrofolate (r = 0.455, p = 0.026) and dimethylglycine (DMG; r = -0.386, p = 0.047). Subjects in the group A with RTL above the median had lower MMA and higher choline compared to subjects below the median.
  
  
  CONCLUSIONS
  The present pilot study suggests a functional relationship between one-carbon metabolism and telomere length. This conclusion is supported by several correlations that were modified by B-vitamin supplementation. In agreement with our hypothesis, the availability of nucleotides and methylation groups seems to impact telomere length. Due to the small sample size and the limitations of the study, further studies should confirm the present results in a larger cohort.
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Pusceddu
authors.affiliation: Department of Clinical Pathology, District Hospital Bolzano, Bolzano, Italy.
authors.forename: Markus
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Kirsch
authors.affiliation: Department of Cardiology, Saarland University Hospital, Homburg/Saar, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Werner
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hübner
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Bodis
authors.affiliation: Department of Cardiology, Saarland University Hospital, Homburg/Saar, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
authors.affiliation: Department of Oncology, Asklepiosklinik Triberg, Triberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Widmann
authors.affiliation: Institute for Medical Biometry, Epidemiology and Medical Informatics, Saarland University, Homburg/Saar, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagenpfeil
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisel
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany. w-herrmann@gmx.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herrmann
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002119:Calcium Carbonate / Q000008:administration & dosage; D002244:Carbon / Q000378:metabolism*; D002794:Choline / Q000097:blood; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics; D008764:Methylmalonic Acid / Q000097:blood; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012521:Sarcosine / Q000031:analogs & derivatives / Q000097:blood; D016615:Telomere / Q000648:ultrastructure*; D059505:Telomere Homeostasis; D013763:Tetrahydrofolates / Q000097:blood; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000097:blood; D025101:Vitamin B 6 / Q000008:administration & dosage / Q000097:blood; D014803:Vitamin B Complex / Q000008:administration & dosage* / Q000097:blood; D014807:Vitamin D / Q000008:administration & dosage* / Q000097:blood
chemical_list: D015415:Biomarkers; D013763:Tetrahydrofolates; D014803:Vitamin B Complex; D014807:Vitamin D; D002244:Carbon; C018092:5,10-methenyltetrahydrofolate; C025138:dimethylglycine; D025101:Vitamin B 6; D008764:Methylmalonic Acid; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002119:Calcium Carbonate; D002794:Choline; D014805:Vitamin B 12; C005984:5-methyltetrahydrofolate; D012521:Sarcosine
keywords: One-carbon metabolites; Telomere length; Vitamin B supplementation