The Effect of Serum 25-Hydroxyvitamin D on Elevated Homocysteine Concentrations in Participants of a Preventive Health Program

PLoS One. 2016 Aug 22;11(8):e0161368. doi: 10.1371/journal.pone.0161368. eCollection 2016.


Both lower serum 25-hydroxyvitamin D [25(OH)D] and elevated homocysteine concentrations are potential risk factors for cardiovascular disease (CVD). A recent analysis of the National Health and Nutrition Examination Survey reported an inverse association of serum 25(OH)D with homocysteine, however, the longitudinal relationship has yet to be investigated. We hypothesized and examined whether a temporal increase in 25(OH)D concentrations is paralleled by a reduction in the risk for elevated homocysteine. We analyzed data of 4475 participants with repeated assessments of serum 25(OH)D and homocysteine concentrations who enrolled in a preventive health program that encourages vitamin D supplementation and monitors serum 25(OH)D and homocysteine concentrations. We defined elevated homocysteine as concentrations greater than 13 micromoles per liter. Logistic regression was applied to assess the association of temporal changes in serum 25(OH)D with the risk of elevated homocysteine. We observed an inverse gradient whereby greater increases in 25(OH)D concentrations were associated with a lower prevalence of elevated homocysteine. Relative to those without temporal increases in 25(OH)D, participants who showed improvements in their serum 25(OH)D concentrations of "<25", "25-50", "50-75", and "≥75" nanomoles per liter at follow up were 0.92 (95% confidence interval: 0.62-1.37), 0.52 (0.33-0.80), 0.34 (0.20-0.58), and 0.32 (0.19-0.54) times as likely to have elevated homocysteine, respectively. These observations suggest that temporal improvements in vitamin D status reduce serum homocysteine concentrations, and therefore may potentially contribute to the primary prevention of CVD.

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Dietary Supplements*
  • Female
  • Homocysteine / blood
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Nutrition Surveys
  • Preventive Health Services
  • Primary Prevention*
  • Risk Factors
  • Vitamin D / administration & dosage
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / prevention & control*


  • Homocysteine
  • Vitamin D
  • 25-hydroxyvitamin D

Grant support

This is an analysis of secondary data. The data had been collected for the purpose of lifestyle counseling of participants by a preventive health program. None of the authors were involved in the execution of this program; neither did they provide financial support. PJV holds a Canada Research Chair in Population Health, an Alberta Research Chair in Nutrition and Disease Prevention, and an Alberta Innovates Health Scholarship. The funding for the Canada Research Chair is provided through the Canadian Institutes for Health Research to the University of Alberta. The Alberta Research Chair is awarded by the School of Public Health at the University of Alberta through a thematic research contract with the Pure North S’Energy Foundation. The Health Scholarship is funded by the Alberta provincial government through Alberta Innovates Health Solutions. The funders had no role in analytic design, data analysis, decision to publish, or preparation of this manuscript.