Subclinical inflammation, telomere shortening, homocysteine, vitamin B6, and mortality: the Ludwigshafen Risk and Cardiovascular Health Study

Eur J Nutr. 2020 Jun;59(4):1399-1411. doi: 10.1007/s00394-019-01993-8. Epub 2019 May 25.


Purpose: Short telomeres and B vitamin deficiencies have been proposed as risk factors for age-related diseases and mortality that interact through oxidative stress and inflammation. However, available data to support this concept are insufficient. We aimed to investigate the predictive role of B vitamins and homocysteine (HCY) for mortality in cardiovascular patients. We explored potential relationships between HCY, B vitamins, relative telomere length (RTL), and indices of inflammation.

Methods: Vitamin B6, HCY, interleukin-6 (IL-6), high-sensitive-C-reactive protein (hs-CRP), and RTL were measured in participants of the Ludwigshafen Risk and Cardiovascular Health Study. Death events were recorded over a median follow-up of 9.9 years.

Results: All-cause mortality increased with higher concentrations of HCY and lower vitamin B6. Patients in the 4th quartile of HCY and vitamin B6 had hazard ratios (HR) for all-cause mortality of 2.77 (95% CI 2.28-3.37) and 0.41(95% CI 0.33-0.49), respectively, and for cardiovascular mortality of 2.78 (95% CI 2.29-3.39) and 0.40 (95% CI 0.33-0.49), respectively, compared to those in the 1st quartile. Multiple adjustments for confounders did not change these results. HCY and vitamin B6 correlated with age-corrected RTL (r = - 0.086, p < 0.001; r = 0.04, p = 0.031, respectively), IL-6 (r = 0.148, p < 0.001; r = - 0.249, p < 0.001, respectively), and hs-CRP (r = 0.101, p < 0.001; r = - 0.320, p < 0.001, respectively). Subjects with the longest telomeres had a significantly higher concentration of vitamin B6, but lower concentrations of HCY, IL-6, and hs-CRP. Multiple regression analyses identified HCY as an independent negative predictor of age-corrected RTL.

Conclusions: In conclusion, hyperhomocysteinemia and vitamin B6 deficiency are risk factors for death from any cause. Hyperhomocysteinemia and vitamin B6 deficiency correlate with increased mortality. This correlation might, at least partially, be explained by accelerated telomere shortening induced by oxidative stress and systemic inflammation in these circumstances.

Keywords: Homocysteine; Inflammation; Mortality; Telomere length; Vitamin B6.

MeSH terms

  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / mortality*
  • Female
  • Germany / epidemiology
  • Health Surveys / methods
  • Health Surveys / statistics & numerical data
  • Homocysteine / blood*
  • Humans
  • Inflammation / epidemiology*
  • Male
  • Middle Aged
  • Risk Assessment
  • Telomere Shortening*
  • Vitamin B 6 / blood*


  • Homocysteine
  • Vitamin B 6