One-carbon metabolites and telomere length in a prospective and randomized study of B- and/or D-vitamin supplementation
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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.
In the present randomized intervention study, we investigated whether the one-carbon metabolism is related to telomere length, a surrogate marker for cellular aging.
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.
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.
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.
KeywordsTelomere length Vitamin B supplementation One-carbon metabolites
Relative telomere length
Human telomerase reverse transcriptase
Body mass index
Compliance with ethical standards
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
- 2.Herrmann W, Knapp JP (2002) Hyperhomocysteinemia: a new risk factor for degenerative diseases. Clin Lab 48:471–481Google Scholar
- 3.Herrmann W, Herrmann M, Joseph J, Tyagi SC (2007) Homocysteine, brain natriuretic peptide and chronic heart failure, a critical review. Clin Chem Lab Med 45:1633–1644Google Scholar
- 14.Herrmann W, Kirsch SH, Kruse V, Eckert R, Graber S, Geisel J, Obeid R (2013) One year B and D vitamins supplementation improves metabolic bone markers. Clin Chem Lab Med 51:639–647Google Scholar
- 18.Stabler SP, Lindenbaum J, Savage DG, Allen RH (1993) Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. Blood 81:3404–3413Google Scholar
- 20.Kirsch SH, Knapp JP, Geisel J, Herrmann W, Obeid R (2009) Simultaneous quantification of S-adenosyl methionine and S-adenosyl homocysteine in human plasma by stable-isotope dilution ultra performance liquid chromatography tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 877:3865–3870CrossRefGoogle Scholar
- 22.Kirsch SH, Herrmann W, Rabagny Y, Obeid R (2010) Quantification of acetylcholine, choline, betaine, and dimethylglycine in human plasma and urine using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 878:3338–3344CrossRefGoogle Scholar
- 23.Ulleland M, Eilertsen I, Quadros EV, Rothenberg SP, Fedosov SN, Sundrehagen E, Orning L (2002) Direct assay for cobalamin bound to transcobalamin (holo-transcobalamin) in serum. Clin Chem 48:526–532Google Scholar
- 26.Pusceddu I, Herrmann M, Kirsch SH, Werner C, Hübner U, Bodis M, Laufs U, Wagenpfeil S, Geisel J, Herrmann W (2015) Prospective study of telomere length and LINE-1 methylation in peripheral blood cells: the role of B and/or D vitamins supplementation. Eur J Nutr. doi: 10.1007/500394-015-1003-1 Google Scholar
- 32.Bull CF, Mayrhofer G, O’Callaghan NJ, Au AY, Pickett HA, Low GKM, Zeegers D, Hande MP, Fenech MF (2013) Folate deficiency induces dysfunctional long and short telomeres; both states are associated with hypomethylation and DNA damage in human WIL2-NS cells. Cancer Prev Res 7:128–138CrossRefGoogle Scholar