Day 3 :
Saarland University Hospital, Germany
Keynote: One carbon metabolites and telomere length in cross-sectional, prospective and randomized one year B-/D-Vitamin supplementation trials
Time : 09:30-10:15
Wolfgang Herrmann is completed his Graduatation and Postgraduation from Saarland University and now he is working as Professor, He is also the president of the Technical University of Munich.
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 B12, B6 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 B12, B6, 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 with HCY (r=-0.151; p=0.007). RTL was shorter in the presence of hyperhomocysteinemia. HCY was 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 B6, B12, 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.
Connolly Hospital, Ireland
Dr. Conor Kerley has his expertise in chronic disease prevention and treatment. Dr. Kerley received his Bachelor’s degree in Human Nutrition and Dietetics from Trinity College Dublin and his PhD from University College Dublin. He has presented his award winning findings at multiple national and international nutrition and medical conferences. His research has been published in international peer-reviewed medical journals and has attracted over €210,000 in research funding to date In addition to his clinical research, He served as chairperson of the Scientific and Research Steering Group of the Irish Nutrition and Dietetics Institute and is an active member of several professional societies including the Irish Nutrition and Dietetics Institute, Nutrition Society, The National Blood Pressure Council and The True Health Initiative. The current work is based on Dr. Kerley’s design and implementation of a novel, innovative nutrition education intervention in addition to an exercise focused rehabilitation program.
Statement of the Problem: Despite medical advance, cardiometabolic pathologies, including cardiac and respiratory diseases are major causes of premature morbidity and mortality worldwide. Cost effective, safe and sustainable therapies are urgently required.
Nitric oxide (NO) is a potent vasodilator. NO synthesis can be facilitated in vivo by reduction of dietary nitrate (NO3-) to NO independent of NO synthase, possibly providing therapeutic effect. Multiple cardiometabolic pathologies are associated with perturbations in NO, including hypertension (HTN) and obstructive sleep apnoea syndrome (OSAS). To extend findings from our preliminary studies (1,2), we hypothesized that dietary NO3- may have utility in HTN and OSAS.
We conducted 2 separate double-blind, randomized, placebo-controlled, crossover trials of daily NO3- supplementation (concentrated beetroot juice) compared to placebo (PL; matching nitrate-depleted beetroot juice) for 14d among a group of well-characterized, treated yet uncontrolled hypertensives(3) and subjects with newly diagnosed OSAS(4).
We recruited 20 uncontrolled hypertensives (mean age=63y, mean BMI=31kg/m2, mean no. of antihypertensives=2) as well as 12 adults with severe OSAS (mean apnoea-hypnoea index=74, mean age=52y, mean BMI=31kg/m2). Assessments were conducted on three occasions, baseline (day 1), midpoint, (day 15) and endpoint (day 29) - before and after each intervention period and included plasma nitrate as well as 24h ambulatory blood pressure (table 1).
Daily dietary nitrate was well-tolerated, safe, led to increased plasma NO metabolites and decreased BP profiles in uncontrolled hypertensives and OSAS. Dietary nitrate has potential as a novel therapeutic, adjunct strategy in difficult to treat BP.. In a review review, we wrote that ‘increased green vegetables consumption may provide similar/ superior benefits to nitrate supplementation in a cheaper, safer, and potentially tastier context’ (5). Considering the low cost and safety profile of foods containing dietary nitrate, this concept appears promising as an adjunct therapeutic strategy for elevated blood pressure