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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.

Design

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.

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Abbreviations

RTL:

Relative telomere length

MTHFR:

5,10-Methylenetetrahydrofolate reductase

5-methylTHF:

5-Methyltetrahydrofolate

MMA:

Methylmalonic acid

5,10-MTHF:

5,10-Methenyltetrahydrofolate

DMG:

Dimethylglycine

tHcy:

Homocysteine

SAM:

S-adenosylmethionine

SAH:

S-adenosylhomocysteine

hTERT:

Human telomerase reverse transcriptase

CYS:

Cystathionine

BMI:

Body mass index

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Correspondence to Wolfgang Herrmann.

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Pusceddu, I., Herrmann, M., Kirsch, S.H. et al. One-carbon metabolites and telomere length in a prospective and randomized study of B- and/or D-vitamin supplementation. Eur J Nutr 56, 1887–1898 (2017). https://doi.org/10.1007/s00394-016-1231-z

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Keywords

  • Telomere length
  • Vitamin B supplementation
  • One-carbon metabolites