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Volume 8
Journal of Nutrition & Food Sciences
ISSN: 2155-9600
Nutrition Congress 2018
June 11-13, 2018
Page 65
conference
series
.com
June 11-13, 2018 | Dublin, Ireland
21
st
European
Nutrition and Dietetics Conference
Wolfgang Herrmann, J Nutr Food Sci 2018, Volume 8
DOI: 10.4172/2155-9600-C3-058
One carbon metabolites and telomere length in cross-sectional, prospective and randomized one
year B-/D-Vitamin supplementation trials
Background:
Telomeres are essential for the maintenance of genomic integrity. Telomere length declines with age and telomere
dysfunction has been proposed as a biomarker for age-related diseases. Vitamin B
12
, B
6
and folic acid are essential cofactors
for numerous cellular processes including the synthesis of purines and nucleotides, DNA and protein methylation. B vitamin
deficiencies and hyperhomocysteinemia are risk factors for the development of age-related diseases. The aim of this study is to
evaluate the effects of B vitamins on telomere biology.
Methods:
We analyzed the LURIC study (3316 cardiovascular patients), the South-Tyrolean study (STVS, 350 healthy subjects) and
the KNOVIB study (60 elderly subjects were supplemented for one year with vitamin B
12
, B
6
, folate, vitamin D and calcium (group
A n=31) or only with vitamin D and calcium (group B n=29)). Relative Telomere Length (RTL), LINE-1 methylation, vitamin
B6, B9, B12, Homocysteine (HCY), 5-methyltetrahydrofolate (5-methylTHF), 5,10-methenylTHF, S-adenosylhomocysteine,
S-adenosylmethionine (SAM), cystathionine, dimethyl-glycine, metylmalonic acid, choline, IL-6, C-Reactive Protein (CRP) and
advanced glycation end-products (AGEs) were quantified.
Results:
Median HCY was 9.8 μmol/L in the STVS and 12.4 μmol/L in the LURIC study. Age-corrected RTL correlated negatively
withHCY (r=-0.151; p=0.007). RTLwas shorter in the presence of hyperhomocysteinemia. HCYwas also lower in the highest (4th)
quartile of age-corrected RTL. In the LURIC study, age-corrected RTL correlated positively with vitamin B6 (r=0.04; p=0.031),
and the 4th quartile of age-corrected RTL was characterized by higher levels of vitamins B6 and folic acid and by lower levels of
IL-6 and hsCRP. Age-corrected RTL correlated negatively with IL-6 (r=-0.043; p=0.019). IL-6 and hsCRP correlated negatively
with vitamin B6, folic acid, and positively with HCY. In the STVS age-corrected RTL correlated negatively with AGEs (r=-0.146,
p=0.01). AGEs correlated positively with HCY and negatively with vitamin B12. In fact, AGEs were higher in subjects with
vitamin B12 below the median. In the interventional study, at baseline HCY and 5-methylTHF were significant predictors of RTL.
Vitamins supplementation decreased HCY in group A but not in group B. Vitamins supplementation in group A increased LINE-
1-methylation but reduced it in group B. After supplementation in group B but not in group A LINE-1-methylation correlated
inversely with RTL, and LINE-1-methylation variation was an independent predictor of RTL variations. In group B an increase in
RTL was correlated with lower LINE-1-methylation. Subjects with 5-methylTHF >10nmol/L had compared with <10nmol/L at
baseline lower LINE-1-methylation, due to a to a lower SAM formation. Subjects with HCY >12µmol/L had compared <12µmol/L
at baseline and after supplementation longer telomeres. In group B subjects with HCY >12µmol/L had lower mean LINE-1-
methylation. Multiple backward regression analysis showed, 5-methylTHF in group A and HCY in group B were significant
predictors for LINE-1-methylation.
Conclusions:
The results from these studies provide evidence for an association between vitamin B
6
, B
12
, folic acid, HCY and
telomere length. Hyperhomocysteinemia is able to negatively affect telomere length in healthy, in cardiovascular patients and in
elderly. On one hand hyperhomocysteinemia is able to induce an inflammatory and oxidant status that in turn induces telomere
attrition. On the other hand hyperhomocysteinemia induces DNA hypomethylation that in turn induces telomere dysfunction.
In fact, literature data indicates that DNA hypomethylation is associated with elongated and dysfunctional telomeres. Further
analyses are needed to confirm these results.
Wolfgang Herrmann
Saarland University Hospital, Germany